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Formins, Golgi, and the Centriole

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The Golgi Apparatus and Centriole

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 67))

Abstract

Formin homology proteins (formins) are a highly conserved family of cytoskeletal remodeling proteins that are involved in a diverse array of cellular functions. Formins are best known for their ability to regulate actin dynamics, but the same functional domains also govern stability and organization of microtubules. It is thought that this dual activity allows them to coordinate the activity of these two major cytoskeletal networks and thereby influence cellular architecture. Golgi ribbon assembly is dependent upon cooperative interactions between actin filaments and cytoplasmic microtubules originating both at the Golgi itself and from the centrosome. Similarly, centrosome assembly, centriole duplication, and centrosome positioning are also reliant on a dialogue between both cytoskeletal networks. As presented in this chapter, a growing body of evidence suggests that multiple formin proteins play essential roles in these central cellular processes.

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References

  • Adler PN, Wallingford JB (2017) From planar cell polarity to ciliogenesis and back: the curious tale of the PPE and CPLANE proteins. Trends Cell Biol 27:379–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agircan FG, Schiebel E, Mardin BR (2014) Separate to operate: control of centrosome positioning and separation. Philos Trans R Soc Lond Ser B Biol Sci 369

    Article  CAS  Google Scholar 

  • Alberts AS (2001) Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain. J Biol Chem 276:2824–2830

    Article  CAS  PubMed  Google Scholar 

  • Andres-Delgado L, Anton OM, Bartolini F, Ruiz-Saenz A, Correas I, Gundersen GG, Alonso MA (2012) INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells. J Cell Biol 198:1025–1037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andres-Delgado L, Anton OM, Alonso MA (2013) Centrosome polarization in T cells: a task for formins. Front Immunol 4:191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ang SF, Zhao ZS, Lim L, Manser E (2010) DAAM1 is a formin required for centrosome re-orientation during cell migration. PLoS One 5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arden JD, Lavik KI, Rubinic KA, Chiaia N, Khuder SA, Howard MJ, Nestor-Kalinoski AL, Alberts AS, Eisenmann KM (2015) Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy. Mol Biol Cell 26:3704–3718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aspenstrom P, Richnau N, Johansson AS (2006) The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics. Exp Cell Res 312:2180–2194

    Article  PubMed  CAS  Google Scholar 

  • Bartolini F, Gundersen GG (2010) Formins and microtubules. Biochim Biophys Acta 1803:164–173

    Article  CAS  PubMed  Google Scholar 

  • Bartolini F, Moseley JB, Schmoranzer J, Cassimeris L, Goode BL, Gundersen GG (2008) The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. J Cell Biol 181:523–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartolini F, Ramalingam N, Gundersen GG (2012) Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1. Mol Biol Cell 23:4032–4040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartolini F, Andres-Delgado L, Qu X, Nik S, Ramalingam N, Kremer L, Alonso MA, Gundersen GG (2016) An mDia1-INF2 formin activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells. Mol Biol Cell 27:1797–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beli P, Mascheroni D, Xu D, Innocenti M (2008) WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2. Nat Cell Biol 10:849–857

    Article  CAS  PubMed  Google Scholar 

  • Bisel B, Wang Y, Wei JH, Xiang Y, Tang D, Miron-Mendoza M, Yoshimura S, Nakamura N, Seemann J (2008) ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65. J Cell Biol 182:837–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Block J, Breitsprecher D, Kuhn S, Winterhoff M, Kage F, Geffers R, Duwe P, Rohn JL, Baum B, Brakebusch C, Geyer M, Stradal TE, Faix J, Rottner K (2012) FMNL2 drives actin-based protrusion and migration downstream of Cdc42. Curr Biol 22:1005–1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castrillon DH, Wasserman SA (1994) Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 120:3367–3377

    CAS  PubMed  Google Scholar 

  • Chan MW, Chaudary F, Lee W, Copeland JW, McCulloch CA (2010) Force-induced myofibroblast differentiation through collagen receptors is dependent on mammalian diaphanous (mDia). J Biol Chem 285:9273–9281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng L, Zhang J, Ahmad S, Rozier L, Yu H, Deng H, Mao Y (2011) Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev Cell 20:342–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chhabra ES, Ramabhadran V, Gerber SA, Higgs HN (2009) INF2 is an endoplasmic reticulum-associated formin protein. J Cell Sci 122:1430–1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chi X, Wang S, Huang Y, Stamnes M, Chen JL (2013) Roles of rho GTPases in intracellular transport and cellular transformation. Int J Mol Sci 14:7089–7108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colon-Franco JM, Gomez TS, Billadeau DD (2011) Dynamic remodeling of the actin cytoskeleton by FMNL1gamma is required for structural maintenance of the Golgi complex. J Cell Sci 124:3118–3126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Copeland JW, Copeland SJ, Treisman R (2004) Homo-oligomerization is essential for F-actin assembly by the formin family FH2 domain. J Biol Chem 279:50250–50256

    Article  CAS  PubMed  Google Scholar 

  • Copeland SJ, Green BJ, Burchat S, Papalia GA, Banner D, Copeland JW (2007) The diaphanous inhibitory domain/diaphanous autoregulatory domain interaction is able to mediate heterodimerization between mDia1 and mDia2. J Biol Chem 282:30120–30130

    Article  CAS  PubMed  Google Scholar 

  • Copeland SJ, Thurston SF, Copeland JW (2016) Actin- and microtubule-dependent regulation of Golgi morphology by FHDC1. Mol Biol Cell 27:260–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Copeland SJ, McRae A, Guarguaglini G, Trinkle-Mulcahy L, Copeland JW (2018) Actin-dependent regulation of cilia length by the inverted formin FHDC1. Mol Biol Cell 29:1611–1627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Courtemanche N (2018) Mechanisms of formin-mediated actin assembly and dynamics. Biophys Rev 10:1553–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Courtemanche N, Lee JY, Pollard TD, Greene EC (2013) Tension modulates actin filament polymerization mediated by formin and profilin. Proc Natl Acad Sci U S A 110:9752–9757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egea G, Serra-Peinado C, Salcedo-Sicilia L, Gutierrez-Martinez E (2013) Actin acting at the Golgi. Histochem Cell Biol 140:347–360

    Article  CAS  PubMed  Google Scholar 

  • Eisenmann KM, West RA, Hildebrand D, Kitchen SM, Peng J, Sigler R, Zhang J, Siminovitch KA, Alberts AS (2007) T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice. J Biol Chem 282:25152–25158

    Article  CAS  PubMed  Google Scholar 

  • Ercan-Sencicek AG, Jambi S, Franjic D, Nishimura S, Li M, El-Fishawy P, Morgan TM, Sanders SJ, Bilguvar K, Suri M, Johnson MH, Gupta AR, Yuksel Z, Mane S, Grigorenko E, Picciotto M, Alberts AS, Gunel M, Sestan N, State MW (2015) Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans. Eur J Hum Genet 23:165–172

    Article  PubMed  CAS  Google Scholar 

  • Esue O, Harris ES, Higgs HN, Wirtz D (2008) The filamentous actin cross-linking/bundling activity of mammalian formins. J Mol Biol 384:324–334

    Article  CAS  PubMed  Google Scholar 

  • Farazi TA, Waksman G, Gordon JI (2001) The biology and enzymology of protein N-myristoylation. J Biol Chem 276:39501–39504

    Article  CAS  PubMed  Google Scholar 

  • Farhan H, Hsu VW (2016) Cdc42 and cellular polarity: emerging roles at the Golgi. Trends Cell Biol 26:241–248

    Article  CAS  PubMed  Google Scholar 

  • Farina F, Gaillard J, Guerin C, Coute Y, Sillibourne J, Blanchoin L, Thery M (2016) The centrosome is an actin-organizing centre. Nat Cell Biol 18:65–75

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Barrera J, Alonso MA (2018) Coordination of microtubule acetylation and the actin cytoskeleton by formins. Cell Mol Life Sci 75:3181–3191

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Barrera J, Bernabe-Rubio M, Casares-Arias J, Rangel L, Fernandez-Martin L, Correas I, Alonso MA (2018) The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via alpha-TAT1 gene expression. J Cell Biol 217:929–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gadadhar S, Bodakuntla S, Natarajan K, Janke C (2017) The tubulin code at a glance. J Cell Sci 130:1347–1353

    Article  CAS  PubMed  Google Scholar 

  • Gaillard J, Ramabhadran V, Neumanne E, Gurel P, Blanchoin L, Vantard M, Higgs HN (2011) Differential interactions of the formins INF2, mDia1, and mDia2 with microtubules. Mol Biol Cell 22:4575–4587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gardberg M, Talvinen K, Kaipio K, Iljin K, Kampf C, Uhlen M, Carpen O (2010) Characterization of Diaphanous-related formin FMNL2 in human tissues. BMC Cell Biol 11:55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gasteier JE, Madrid R, Krautkramer E, Schroder S, Muranyi W, Benichou S, Fackler OT (2003) Activation of the Rac-binding partner FHOD1 induces actin stress fibers via a ROCK-dependent mechanism. J Biol Chem 278:38902–38912

    Article  CAS  PubMed  Google Scholar 

  • Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD (2007) Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 26:177–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorelik R, Yang C, Kameswaran V, Dominguez R, Svitkina T (2011) Mechanisms of plasma membrane targeting of formin mDia2 through its amino terminal domains. Mol Biol Cell 22:189–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould CJ, Maiti S, Michelot A, Graziano BR, Blanchoin L, Goode BL (2011) The formin DAD domain plays dual roles in autoinhibition and actin nucleation. Curr Biol 21:384–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grobe H, Wustenhagen A, Baarlink C, Grosse R, Grikscheit K (2018) A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. PLoS One 13:e0194716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guarguaglini G, Duncan PI, Stierhof YD, Holmstrom T, Duensing S, Nigg EA (2005) The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles. Mol Biol Cell 16:1095–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guillabert-Gourgues A, Jaspard-Vinassa B, Bats ML, Sewduth RN, Franzl N, Peghaire C, Jeanningros S, Moreau C, Roux E, Larrieu-Lahargue F, Dufourcq P, Couffinhal T, Duplaa C (2016) Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity-signaling pathway. Mol Biol Cell 27:941–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurel PS, Ge P, Grintsevich EE, Shu R, Blanchoin L, Zhou ZH, Reisler E, Higgs HN (2014) INF2-mediated severing through actin filament encirclement and disruption. Curr Biol 24:156–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Habas R, Kato Y, He X (2001) Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 107:843–854

    Article  CAS  PubMed  Google Scholar 

  • Han Y, Eppinger E, Schuster IG, Weigand LU, Liang X, Kremmer E, Peschel C, Krackhardt AM (2009) Formin-like 1 (FMNL1) is regulated by N-terminal myristoylation and induces polarized membrane blebbing. J Biol Chem 284:33409–33417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris ES, Li F, Higgs HN (2004) The mouse formin, FRLalpha, slows actin filament barbed end elongation, competes with capping protein, accelerates polymerization from monomers, and severs filaments. J Biol Chem 279:20076–20087

    Article  CAS  PubMed  Google Scholar 

  • Harris ES, Rouiller I, Hanein D, Higgs HN (2006) Mechanistic differences in actin bundling activity of two mammalian formins, FRL1 and mDia2. J Biol Chem 281:14383–14392

    Article  CAS  PubMed  Google Scholar 

  • Harris ES, Gauvin TJ, Heimsath EG, Higgs HN (2010) Assembly of filopodia by the formin FRL2 (FMNL3). Cytoskeleton (Hoboken) 67:755–772

    Article  CAS  Google Scholar 

  • Hegsted A, Yingling CV, Pruyne D (2017) Inverted formins: a subfamily of atypical formins. Cytoskeleton 74:405–419

    Article  PubMed  Google Scholar 

  • Heimsath EG Jr, Higgs HN (2012) The C terminus of formin FMNL3 accelerates actin polymerization and contains a WH2 domain-like sequence that binds both monomers and filament barbed ends. J Biol Chem 287:3087–3098

    Article  CAS  PubMed  Google Scholar 

  • Henty-Ridilla JL, Rankova A, Eskin JA, Kenny K, Goode BL (2016) Accelerated actin filament polymerization from microtubule plus ends. Science 352:1004–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y, Narumiya S, Watanabe N (2004) Actin polymerization-driven molecular movement of mDia1 in living cells. Science 303:2007–2010

    Article  CAS  PubMed  Google Scholar 

  • Higashida C, Kiuchi T, Akiba Y, Mizuno H, Maruoka M, Narumiya S, Mizuno K, Watanabe N (2013) F- and G-actin homeostasis regulates mechanosensitive actin nucleation by formins. Nat Cell Biol 15:395–405

    Article  CAS  PubMed  Google Scholar 

  • Higgs HN (2005) Formin proteins: a domain-based approach. Trends Biochem Sci 30:342–353

    Article  CAS  PubMed  Google Scholar 

  • Hotulainen P, Lappalainen P (2006) Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol 173:383–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurtado L, Caballero C, Gavilan MP, Cardenas J, Bornens M, Rios RM (2011) Disconnecting the Golgi ribbon from the centrosome prevents directional cell migration and ciliogenesis. J Cell Biol 193:917–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishizaki T, Morishima Y, Okamoto M, Furuyashiki T, Kato T, Narumiya S (2001) Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Nat Cell Biol 3:8–14

    Article  CAS  PubMed  Google Scholar 

  • Iskratsch T, Lange S, Dwyer J, Kho AL, dos Remedios C, Ehler E (2010) Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance. J Cell Biol 191:1159–1172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isogai T, van der Kammen R, Innocenti M (2015) SMIFH2 has effects on Formins and p53 that perturb the cell cytoskeleton. Sci Rep 5:9802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ito D, Bettencourt-Dias M (2018) Centrosome remodelling in evolution. Cells 7

    Google Scholar 

  • Jegou A, Carlier MF, Romet-Lemonne G (2013) Formin mDia1 senses and generates mechanical forces on actin filaments. Nat Commun 4:1883

    Article  PubMed  CAS  Google Scholar 

  • Ju R, Cirone P, Lin S, Griesbach H, Slusarski DC, Crews CM (2010) Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis. Proc Natl Acad Sci U S A 107:6906–6911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kage F, Steffen A, Ellinger A, Ranftler C, Gehre C, Brakebusch C, Pavelka M, Stradal T, Rottner K (2017) FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42. Sci Rep 7:9791

    Article  PubMed  PubMed Central  Google Scholar 

  • Kitzing TM, Wang Y, Pertz O, Copeland JW, Grosse R (2010) Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene 29:2441–2448

    Article  CAS  PubMed  Google Scholar 

  • Kobielak A, Pasolli HA, Fuchs E (2004) Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables. Nat Cell Biol 6:21–30

    Article  CAS  PubMed  Google Scholar 

  • Kodani A, Kristensen I, Huang L, Sutterlin C (2009) GM130-dependent control of Cdc42 activity at the Golgi regulates centrosome organization. Mol Biol Cell 20:1192–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong D, Farmer V, Shukla A, James J, Gruskin R, Kiriyama S, Loncarek J (2014) Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles. J Cell Biol 206:855–865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovar DR, Pollard TD (2004) Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc Natl Acad Sci U S A 101:14725–14730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kozlov MM, Bershadsky AD (2004) Processive capping by formin suggests a force-driven mechanism of actin polymerization. J Cell Biol 167:1011–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuhn S, Geyer M (2014) Formins as effector proteins of Rho GTPases. Small GTPases 5:e29513

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kuhn S, Erdmann C, Kage F, Block J, Schwenkmezger L, Steffen A, Rottner K, Geyer M (2015) The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation. Nat Commun 6:7088

    Article  PubMed  CAS  Google Scholar 

  • Kutscheidt S, Zhu R, Antoku S, Luxton GW, Stagljar I, Fackler OT, Gundersen GG (2014) FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement. Nat Cell Biol 16:708–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • LaMonica K, Bass M, Grabel L (2009) The planar cell polarity pathway directs parietal endoderm migration. Dev Biol 330:44–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee K, Gallop JL, Rambani K, Kirschner MW (2010) Self-assembly of filopodia-like structures on supported lipid bilayers. Science 329:1341–1345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li F, Higgs HN (2003) The mouse Formin mDia1 is a potent actin nucleation factor regulated by autoinhibition. Curr Biol 13:1335–1340

    Article  CAS  PubMed  Google Scholar 

  • Li F, Higgs HN (2005) Dissecting requirements for auto-inhibition of actin nucleation by the formin, mDia1. J Biol Chem 280:6986–6992

    Article  CAS  PubMed  Google Scholar 

  • Lin YN, Windhorst S (2016) Diaphanous-related formin 1 as a target for tumor therapy. Biochem Soc Trans 44:1289–1293

    Article  CAS  PubMed  Google Scholar 

  • Loncarek J, Bettencourt-Dias M (2018) Building the right centriole for each cell type. J Cell Biol 217:823–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long M, Simpson JC (2017) Rho GTPases operating at the Golgi complex: implications for membrane traffic and cancer biology. Tissue Cell 49:163–169

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Meng W, Poy F, Maiti S, Goode BL, Eck MJ (2007) Structure of the FH2 domain of Daam1: implications for formin regulation of actin assembly. J Mol Biol 369:1258–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madrid R, Aranda JF, Rodriguez-Fraticelli AE, Ventimiglia L, Andres-Delgado L, Shehata M, Fanayan S, Shahheydari H, Gomez S, Jimenez A, Martin-Belmonte F, Byrne JA, Alonso MA (2010) The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2. Dev Cell 18:814–827

    Article  CAS  PubMed  Google Scholar 

  • Magdalena J, Millard TH, Machesky LM (2003) Microtubule involvement in NIH 3T3 Golgi and MTOC polarity establishment. J Cell Sci 116:743–756

    Article  CAS  PubMed  Google Scholar 

  • Maiti S, Michelot A, Gould C, Blanchoin L, Sokolova O, Goode BL (2012) Structure and activity of full-length formin mDia1. Cytoskeleton (Hoboken) 69:393–405

    Article  CAS  Google Scholar 

  • Miller PM, Folkmann AW, Maia AR, Efimova N, Efimov A, Kaverina I (2009) Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells. Nat Cell Biol 11:1069–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizuno H, Watanabe N (2012) mDia1 and formins: screw cap of the actin filament. Biophysics (Nagoya-shi) 8:95–102

    Article  CAS  Google Scholar 

  • Mizuno H, Higashida C, Yuan Y, Ishizaki T, Narumiya S, Watanabe N (2011) Rotational movement of the formin mDia1 along the double helical strand of an actin filament. Science 331:80–83

    Article  CAS  PubMed  Google Scholar 

  • Moriya K, Yamamoto T, Takamitsu E, Matsunaga Y, Kimoto M, Fukushige D, Kimoto C, Suzuki T, Utsumi T (2012) Protein N-myristoylation is required for cellular morphological changes induced by two formin family proteins, FMNL2 and FMNL3. Biosci Biotechnol Biochem 76:1201–1209

    Article  CAS  PubMed  Google Scholar 

  • Moseley JB, Sagot I, Manning AL, Xu Y, Eck MJ, Pellman D, Goode BL (2004) A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol Biol Cell 15:896–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moseley JB, Bartolini F, Okada K, Wen Y, Gundersen GG, Goode BL (2007) Regulated binding of adenomatous polyposis coli protein to actin. J Biol Chem 282:12661–12668

    Article  CAS  PubMed  Google Scholar 

  • Nakamura N, Wei JH, Seemann J (2012) Modular organization of the mammalian Golgi apparatus. Curr Opin Cell Biol 24:467–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nezami AG, Poy F, Eck MJ (2006) Structure of the autoinhibitory switch in formin mDia1. Structure 14:257–263

    Article  CAS  PubMed  Google Scholar 

  • Nezami A, Poy F, Toms A, Zheng W, Eck MJ (2010) Crystal structure of a complex between amino and carboxy terminal fragments of mDia1: insights into autoinhibition of diaphanous-related formins. PLoS One 5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nieuwenhuis J, Brummelkamp TR (2019) The tubulin detyrosination cycle: function and enzymes. Trends Cell Biol 29:80–92

    Article  CAS  PubMed  Google Scholar 

  • Okada K, Bartolini F, Deaconescu AM, Moseley JB, Dogic Z, Grigorieff N, Gundersen GG, Goode BL (2010) Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. J Cell Biol 189:1087–1096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otomo T, Otomo C, Tomchick DR, Machius M, Rosen MK (2005) Structural basis of Rho GTPase-mediated activation of the formin mDia1. Mol Cell 18:273–281

    Article  CAS  PubMed  Google Scholar 

  • Palazzo AF, Cook TA, Alberts AS, Gundersen GG (2001) mDia mediates Rho-regulated formation and orientation of stable microtubules. Nat Cell Biol 3:723–729

    Article  CAS  PubMed  Google Scholar 

  • Paran Y, Lavelin I, Naffar-Abu-Amara S, Winograd-Katz S, Liron Y, Geiger B, Kam Z (2006) Development and application of automatic high-resolution light microscopy for cell-based screens. Methods Enzymol 414:228–247

    Article  CAS  PubMed  Google Scholar 

  • Peladeau C, Heibein A, Maltez MT, Copeland SJ, Copeland JW (2016) A specific FMNL2 isoform is up-regulated in invasive cells. BMC Cell Biol 17:32

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peng J, Kitchen SM, West RA, Sigler R, Eisenmann KM, Alberts AS (2007) Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian diaphanous related formin mDia1. Cancer Res 67:7565–7571

    Article  CAS  PubMed  Google Scholar 

  • Petry S, Vale RD (2015) Microtubule nucleation at the centrosome and beyond. Nat Cell Biol 17:1089–1093

    Article  CAS  PubMed  Google Scholar 

  • Pring M, Evangelista M, Boone C, Yang C, Zigmond SH (2003) Mechanism of formin-induced nucleation of actin filaments. Biochemistry 42:486–496

    Article  CAS  PubMed  Google Scholar 

  • Quinlan ME, Hilgert S, Bedrossian A, Mullins RD, Kerkhoff E (2007) Regulatory interactions between two actin nucleators, Spire and Cappuccino. J Cell Biol 179:117–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramabhadran V, Korobova F, Rahme GJ, Higgs HN (2011) Splice variant-specific cellular function of the formin INF2 in maintenance of Golgi architecture. Mol Biol Cell 22:4822–4833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramabhadran V, Gurel PS, Higgs HN (2012) Mutations to the formin homology 2 domain of INF2 protein have unexpected effects on actin polymerization and severing. J Biol Chem 287:34234–34245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramabhadran V, Hatch AL, Higgs HN (2013) Actin monomers activate inverted formin 2 by competing with its autoinhibitory interaction. J Biol Chem 288:26847–26855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rios RM (2014) The centrosome-Golgi apparatus nexus. Philos Trans R Soc Lond Ser B Biol Sci 369

    Article  CAS  Google Scholar 

  • Romero S, Le Clainche C, Didry D, Egile C, Pantaloni D, Carlier MF (2004) Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 119:419–429

    Article  CAS  PubMed  Google Scholar 

  • Rose R, Weyand M, Lammers M, Ishizaki T, Ahmadian MR, Wittinghofer A (2005) Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature 435:513–518

    Article  CAS  PubMed  Google Scholar 

  • Roth-Johnson EA, Vizcarra CL, Bois JS, Quinlan ME (2014) Interaction between microtubules and the Drosophila formin Cappuccino and its effect on actin assembly. J Biol Chem 289:4395–4404

    Article  CAS  PubMed  Google Scholar 

  • Sarmiento C, Wang W, Dovas A, Yamaguchi H, Sidani M, El-Sibai M, Desmarais V, Holman HA, Kitchen S, Backer JM, Alberts A, Condeelis J (2008) WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. J Cell Biol 180:1245–1260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schonichen A, Geyer M (2010) Fifteen formins for an actin filament: a molecular view on the regulation of human formins. Biochim Biophys Acta 1803:152–163

    Article  PubMed  CAS  Google Scholar 

  • Schulze N, Graessl M, Blancke Soares A, Geyer M, Dehmelt L, Nalbant P (2014) FHOD1 regulates stress fiber organization by controlling transversal arc and dorsal fiber dynamics. J Cell Sci 127:1379–1393

    Article  CAS  PubMed  Google Scholar 

  • Scott BJ, Neidt EM, Kovar DR (2011) The functionally distinct fission yeast formins have specific actin-assembly properties. Mol Biol Cell 22:3826–3839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seth A, Otomo C, Rosen MK (2006) Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLalpha and mDia1. J Cell Biol 174:701–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Zhang J, Mullin M, Dong B, Alberts AS, Siminovitch KA (2009) The mDial formin is required for neutrophil polarization, migration, and activation of the LARG/RhoA/ROCK signaling axis during chemotaxis. J Immunol 182:3837–3845

    Article  CAS  PubMed  Google Scholar 

  • Shimada A, Nyitrai M, Vetter IR, Kuhlmann D, Bugyi B, Narumiya S, Geeves MA, Wittinghofer A (2004) The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization. Mol Cell 13:511–522

    Article  CAS  PubMed  Google Scholar 

  • Shinohara R, Thumkeo D, Kamijo H, Kaneko N, Sawamoto K, Watanabe K, Takebayashi H, Kiyonari H, Ishizaki T, Furuyashiki T, Narumiya S (2012) A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors. Nat Neurosci 15:373–380, S371–372

    Article  CAS  PubMed  Google Scholar 

  • Silkworth WT, Kunes KL, Nickel GC, Phillips ML, Quinlan ME, Vizcarra CL (2018) The neuron-specific formin Delphilin nucleates nonmuscle actin but does not enhance elongation. Mol Biol Cell 29:610–621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staus DP, Taylor JM, Mack CP (2011) Enhancement of mDia2 activity by Rho-kinase-dependent phosphorylation of the diaphanous autoregulatory domain. Biochem J 439:57–65

    Article  CAS  PubMed  Google Scholar 

  • Sutterlin C, Colanzi A (2010) The Golgi and the centrosome: building a functional partnership. J Cell Biol 188:621–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeya R, Taniguchi K, Narumiya S, Sumimoto H (2008) The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells. EMBO J 27:618–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson ME, Heimsath EG, Gauvin TJ, Higgs HN, Kull FJ (2013) FMNL3 FH2-actin structure gives insight into formin-mediated actin nucleation and elongation. Nat Struct Mol Biol 20:111–118

    Article  CAS  PubMed  Google Scholar 

  • Thurston SF, Kulacz WA, Shaikh S, Lee JM, Copeland JW (2012) The ability to induce microtubule acetylation is a general feature of formin proteins. PLoS One 7:e48041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thyberg J, Moskalewski S (1985) Microtubules and the organization of the Golgi complex. Exp Cell Res 159:1–16

    Article  CAS  PubMed  Google Scholar 

  • Truong D, Brabant D, Bashkurov M, Wan LC, Braun V, Heo WD, Meyer T, Pelletier L, Copeland J, Brumell JH (2013) Formin-mediated actin polymerization promotes Salmonella invasion. Cell Microbiol 15:2051–2063

    Article  CAS  PubMed  Google Scholar 

  • Vaillant DC, Copeland SJ, Davis C, Thurston SF, Abdennur N, Copeland JW (2008) Interaction of the N- and C-terminal autoregulatory domains of FRL2 does not inhibit FRL2 activity. J Biol Chem 283:33750–33762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valderrama F, Babia T, Ayala I, Kok JW, Renau-Piqueras J, Egea G (1998) Actin microfilaments are essential for the cytological positioning and morphology of the Golgi complex. Eur J Cell Biol 76:9–17

    Article  CAS  PubMed  Google Scholar 

  • Vega FM, Fruhwirth G, Ng T, Ridley AJ (2011) RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J Cell Biol 193:655–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vicente-Manzanares M, Rey M, Perez-Martinez M, Yanez-Mo M, Sancho D, Cabrero JR, Barreiro O, de la Fuente H, Itoh K, Sanchez-Madrid F (2003) The RhoA effector mDia is induced during T cell activation and regulates actin polymerization and cell migration in T lymphocytes. J Immunol 171:1023–1034

    Article  CAS  PubMed  Google Scholar 

  • Vicente-Manzanares M, Zareno J, Whitmore L, Choi CK, Horwitz AF (2007) Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J Cell Biol 176:573–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vicente-Manzanares M, Newell-Litwa K, Bachir AI, Whitmore LA, Horwitz AR (2011) Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells. J Cell Biol 193:381–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinogradova T, Paul R, Grimaldi AD, Loncarek J, Miller PM, Yampolsky D, Magidson V, Khodjakov A, Mogilner A, Kaverina I (2012) Concerted effort of centrosomal and Golgi-derived microtubules is required for proper Golgi complex assembly but not for maintenance. Mol Biol Cell 23:820–833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, El-Zaru MR, Surks HK, Mendelsohn ME (2004) Formin homology domain protein (FHOD1) is a cyclic GMP-dependent protein kinase I-binding protein and substrate in vascular smooth muscle cells. J Biol Chem 279:24420–24426

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Zhang L, Duan X, Zhang GL, Wang ZB, Wang Q, Xiong B, Sun SC (2015) RhoA-mediated FMNL1 regulates GM130 for actin assembly and phosphorylates MAPK for spindle formation in mouse oocyte meiosis. Cell Cycle 14:2835–2843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S (1997) p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 16:3044–3056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe N, Kato T, Fujita A, Ishizaki T, Narumiya S (1999) Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat Cell Biol 1:136–143

    Article  CAS  PubMed  Google Scholar 

  • Werner S, Pimenta-Marques A, Bettencourt-Dias M (2017) Maintaining centrosomes and cilia. J Cell Sci 130:3789–3800

    Article  CAS  PubMed  Google Scholar 

  • Wong YL, Anzola JV, Davis RL, Yoon M, Motamedi A, Kroll A, Seo CP, Hsia JE, Kim SK, Mitchell JW, Mitchell BJ, Desai A, Gahman TC, Shiau AK, Oegema K (2015) Cell biology. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science 348:1155–1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woodham EF, Paul NR, Tyrrell B, Spence HJ, Swaminathan K, Scribner MR, Giampazolias E, Hedley A, Clark W, Kage F, Marston DJ, Hahn KM, Tait SW, Larue L, Brakebusch CH, Insall RH, Machesky LM (2017) Coordination by Cdc42 of actin, contractility, and adhesion for melanoblast movement in mouse skin. Curr Biol 27:624–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woychik RP, Maas RL, Zeller R, Vogt TF, Leder P (1990) ‘Formins’: proteins deduced from the alternative transcripts of the limb deformity gene. Nature 346:850–853

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Akhmanova A (2017) Microtubule-organizing centers. Annu Rev Cell Dev Biol 33:51–75

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Moseley JB, Sagot I, Poy F, Pellman D, Goode BL, Eck MJ (2004) Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture. Cell 116:711–723

    Article  CAS  PubMed  Google Scholar 

  • Yang C, Czech L, Gerboth S, Kojima S, Scita G, Svitkina T (2007) Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol 5:e317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yasunaga T, Hoff S, Schell C, Helmstadter M, Kretz O, Kuechlin S, Yakulov TA, Engel C, Muller B, Bensch R, Ronneberger O, Huber TB, Lienkamp SS, Walz G (2015) The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells. J Cell Biol 211:963–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young KG, Thurston SF, Copeland S, Smallwood C, Copeland JW (2008) INF1 is a novel microtubule-associated formin. Mol Biol Cell 19:5168–5180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaidel-Bar R (2018) Cell cycle pacemaker keeps adhesion in step with division. J Cell Biol 217:2981–2982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng H, Hoover AN, Liu A (2010) PCP effector gene Inturned is an important regulator of cilia formation and embryonic development in mammals. Dev Biol 339:418–428

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Tian Y, Du J, Hu Z, Yang L, Liu J, Gu L (2012) Dvl2-dependent activation of Daam1 and RhoA regulates Wnt5a-induced breast cancer cell migration. PLoS One 7:e37823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zigmond SH, Evangelista M, Boone C, Yang C, Dar AC, Sicheri F, Forkey J, Pring M (2003) Formin leaky cap allows elongation in the presence of tight capping proteins. Curr Biol 13:1820–1823

    Article  CAS  PubMed  Google Scholar 

  • Zilberman Y, Alieva NO, Miserey-Lenkei S, Lichtenstein A, Kam Z, Sabanay H, Bershadsky A (2011) Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics. Mol Biol Cell 22:2900–2911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmermann D, Kovar DR (2019) Feeling the force: formin’s role in mechanotransduction. Curr Opin Cell Biol 56:130–140

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Thanks to S.J. Copeland for preparation of figures. Work in the Copeland lab is supported by NSERC Discovery Grant 05921/RGPIN/2016.

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Copeland, J. (2019). Formins, Golgi, and the Centriole. In: Kloc, M. (eds) The Golgi Apparatus and Centriole. Results and Problems in Cell Differentiation, vol 67. Springer, Cham. https://doi.org/10.1007/978-3-030-23173-6_3

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