Skip to main content

Myosin XIX

  • Chapter
  • First Online:
Myosins

Abstract

The birth of widely available genomic databases at the turn of the millennium led to the identification of many previously unknown myosin genes and identification of novel classes of myosin, including MYO19. Further sequence analysis has revealed the unique evolutionary history of class XIX myosins. MYO19 is found in species ranging from vertebrates to some unicellular organisms, while it has been lost from some lineages containing traditional experimental model organisms. Unique sequences in the motor domain suggest class-specific mechanochemistry that may relate to its cellular function as a mitochondria-associated motor. Work over the past 10 years has demonstrated that MYO19 is an actin-activated ATPase capable of actin-based transport, and investigation of some of the conserved differences within the motor domain indicate their importance in MYO19 motor activity. The cargo-binding MyMOMA tail domain contains two distinct mechanisms of interaction with mitochondrial outer membrane components, and perturbation of MYO19 expression leads to alterations in mitochondrial movement and dynamics that impact cell function. This chapter summarizes the current state of the field and highlights potential new directions of inquiry.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adikes RC, Unrath WC, Yengo CM, Quintero OA (2013) Biochemical and bioinformatic analysis of the myosin-XIX motor domain. Cytoskeleton (Hoboken) 70(5):281–295

    Article  CAS  Google Scholar 

  • Avila F, Mickelson JR, Schaefer RJ, McCue ME (2018) Genome-wide signatures of selection reveal genes associated with performance in American quarter horse subpopulations. Front Genet 9:249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Babenko VA, Silachev DN, Popkov VA, Zorova LD, Pevzner IB, Plotnikov EY, Sukhikh GT, Zorov DB (2018) Miro1 enhances mitochondria transfer from Multipotent Mesenchymal Stem Cells (MMSC) to neural cells and improves the efficacy of cell recovery. Molecules 23(3)

    Article  PubMed Central  CAS  Google Scholar 

  • Babic M, Russo GJ, Wellington AJ, Sangston RM, Gonzalez M, Zinsmaier KE (2015) Miro’s N-terminal GTPase domain is required for transport of mitochondria into axons and dendrites. J Neurosci 35(14):5754–5771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berg JS, Powell BC, Cheney RE (2001) A millennial myosin census. Mol Biol Cell 12(4):780–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bocanegra JL, Fujita BM, Melton NR, Cowan JM, Schinski EL, Tamir TY, Major MB, Quintero OA (2019) The MyMOMA domain of MYO19 encodes for distinct Miro‐dependent and Miro‐independent mechanisms of interaction with mitochondrial membranes. Cytoskeleton (Hoboken), Sep 3. https://doi.org/10.1002/cm.21560

    Article  CAS  PubMed  Google Scholar 

  • Bryan K, McGivney BA, Farries G, McGettigan PA, McGivney CL, Gough KF, MacHugh DE, Katz LM, Hill EW (2017) Equine skeletal muscle adaptations to exercise and training: evidence of differential regulation of autophagosomal and mitochondrial components. BMC Genomics 18(1):595

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Capmany A, Latge B, Schauer K (2019) Analysis of organelle positioning using patterned microdevices. Curr Protoc Cell Biol 82(1):e77

    Article  PubMed  Google Scholar 

  • Catarino CB, Kasperaviciute D, Thom M, Cavalleri GL, Martinian L, Heinzen EL, Dorn T, Grunwald T, Chaila E, Depondt C et al (2011) Genomic microdeletions associated with epilepsy: not a contraindication to resective surgery. Epilepsia 52(8):1388–1392

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheney RE, Mooseker MS (1992) Unconventional myosins. Curr Opin Cell Biol 4(1):27–35

    Article  CAS  PubMed  Google Scholar 

  • Choi YJ, Jung SH, Kim MS, Baek IP, Rhee JK, Lee SH, Hur SY, Kim TM, Chung YJ, Lee SH (2015) Genomic landscape of endometrial stromal sarcoma of uterus. Oncotarget 6(32):33319–33328

    Article  PubMed  PubMed Central  Google Scholar 

  • Cope MJ, Whisstock J, Rayment I, Kendrick-Jones J (1996) Conservation within the myosin motor domain: implications for structure and function. Structure 4(8):969–987

    Article  CAS  PubMed  Google Scholar 

  • Edgren H, Murumagi A, Kangaspeska S, Nicorici D, Hongisto V, Kleivi K, Rye IH, Nyberg S, Wolf M, Borresen-Dale AL et al (2011) Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biol 12(1):R6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fransson S, Ruusala A, Aspenstrom P (2006) The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking. Biochem Biophys Res Commun 344(2):500–510

    Article  CAS  PubMed  Google Scholar 

  • Hawthorne JL, Mehta PR, Singh PP, Wong N, Quintero OA (2016) Positively charged residues within the MYO19 MyMOMA domain are essential for proper localization of MYO19 to the mitochondrial outer membrane. Cytoskeleton 73(6):286–299

    Article  CAS  PubMed  Google Scholar 

  • Hinkes B, Hilgers KF, Bolz HJ, Goppelt-Struebe M, Amann K, Nagl S, Bergmann C, Rascher W, Eckardt KU, Jacobi J (2012) A complex microdeletion 17q12 phenotype in a patient with recurrent de novo membranous nephropathy. BMC Nephrol 13:27

    Article  PubMed  PubMed Central  Google Scholar 

  • Howard J (2001) Mechanics of motor proteins and the cytoskeleton. Sinauer Associates, Sunderland, MA, pp 229–244

    Google Scholar 

  • Hudson TJ, Anderson W, Artez A, Barker AD, Bell C, Bernabe RR, Bhan MK, Calvo F, Eerola I et al (2010) International network of cancer genome projects. Nature 464(7291):993–998

    Google Scholar 

  • Jalali A, Amirian ES, Bainbridge MN, Armstrong GN, Liu Y, Tsavachidis S, Jhangiani SN, Plon SE, Lau CC, Claus EB et al (2015) Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium. Sci Rep 5:8278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katajisto P, Dohla J, Chaffer CL, Pentinmikko N, Marjanovic N, Iqbal S, Zoncu R, Chen W, Weinberg RA, Sabatini DM (2015) Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science 348(6232):340–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10(6):845–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohutek ZA, Rosati LM, Hong J, Poling J, Attiyeh MA, Makohon-Moore A, Herman JM, Iacobuzio-Donahue CA (2017) An unusual genomic variant of pancreatic ductal adenocarcinoma with an indolent clinical course. Cold Spring Harb Mol Case Stud 3(4)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kollmar M, Muhlhausen S (2017) Myosin repertoire expansion coincides with eukaryotic diversification in the Mesoproterozoic era. BMC Evol Biol 17(1):211

    Article  PubMed  PubMed Central  Google Scholar 

  • Lopez-Domenech G, Covill-Cooke C, Ivankovic D, Halff EF, Sheehan DF, Norkett R, Birsa N, Kittler JT (2018) Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution. EMBO J 37(3):321–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Z, Ma XN, Zhang HM, Ji HH, Ding H, Zhang J, Luo D, Sun Y, Li XD (2014) Mouse myosin-19 is a plus-end-directed, high-duty ratio molecular motor. J Biol Chem 289(26):18535–18548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin J, Cooper M, Hamshere ML, Pocklington A, Scherer SW, Kent L, Gill M, Owen MJ, Williams N, O’Donovan MC, et al (2014) Biological overlap of attention-deficit/hyperactivity disorder and autism spectrum disorder: evidence from copy number variants. J Am Acad Child Adolesc Psychiatry 53(7):761–770. e26

    Article  Google Scholar 

  • Menetrey J, Bahloul A, Wells AL, Yengo CM, Morris CA, Sweeney HL, Houdusse A (2005) The structure of the myosin VI motor reveals the mechanism of directionality reversal. Nature 435(7043):779–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30(12):4232–4240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyamoto-Mikami E, Tsuji K, Horii N, Hasegawa N, Fujie S, Homma T, Uchida M, Hamaoka T, Kanehisa H, Tabata I et al (2018) Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men. Sci Rep 8(1):16811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moore AS, Wong YC, Simpson CL, Holzbaur EL (2016) Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks. Nat Commun 7:12886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno-De-Luca D, SGENE Consortium S, Mulle JG, Simons Simplex Collection Genetics Consortium, Kaminsky EB, Sanders SJ, GeneStar MSM, Adam MP, Pakula AT et al (2010) Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 87(5):618–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Novak AJ, Asmann YW, Maurer MJ, Wang C, Slager SL, Hodge LS, Manske M, Price-Troska T, Yang ZZ, Zimmermann MT et al (2015) Whole-exome analysis reveals novel somatic genomic alterations associated with outcome in immunochemotherapy-treated diffuse large B-cell lymphoma. Blood Cancer J 5:e346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odronitz F, Kollmar M (2007) Drawing the tree of eukaryotic life based on the analysis of 2,269 manually annotated myosins from 328 species. Genome Biol 8(9):R196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oeding SJ, Majstrowicz K, Hu XP, Schwarz V, Freitag A, Honnert U, Nikolaus P, Bahler M (2018) Identification of Miro as a mitochondrial receptor for myosin XIX. J Cell Sci

    Google Scholar 

  • Permuth JB, Pirie A, Ann Chen Y, Lin HY, Reid BM, Chen Z, Monteiro A, Dennis J, Mendoza-Fandino G, AOCS Study Group et al (2016) Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk. Hum Mol Genet 25(16):3600–3612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quintero OA, DiVito MM, Adikes RC, Kortan MB, Case LB, Lier AJ, Panaretos NS, Slater SQ, Rengarajan M, Feliu M et al (2009) Human Myo19 is a novel myosin that associates with mitochondria. Curr Biol 19(23):2008–2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reis K, Fransson A, Aspenstrom P (2009) The Miro GTPases: at the heart of the mitochondrial transport machinery. FEBS Lett 583(9):1391–1398

    Article  CAS  PubMed  Google Scholar 

  • Roberts JL, Gandomi SK, Parra M, Lu I, Gau CL, Dasouki M, Butler MG (2014) Clinical report of a 17q12 microdeletion with additionally unreported clinical features. Case Rep Genet 2014:264947

    PubMed  PubMed Central  Google Scholar 

  • Rohn JL, Sims D, Liu T, Fedorova M, Schock F, Dopie J, Vartiainen MK, Kiger AA, Perrimon N, Baum B (2011) Comparative RNAi screening identifies a conserved core metazoan actinome by phenotype. J Cell Biol 194(5):789–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rohn JL, Patel JV, Neumann B, Bulkescher J, McHedlishvili N, McMullan RC, Quintero OA, Ellenberg J, Baum B (2014) Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division. Curr Biol 24(21):2598–2605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russo GJ, Louie K, Wellington A, Macleod GT, Hu F, Panchumarthi S, Zinsmaier KE (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci 29(17):5443–5455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandbacka M, Laivuori H, Freitas E, Halttunen M, Jokimaa V, Morin-Papunen L, Rosenberg C, Aittomaki K (2013) TBX6, LHX1 and copy number variations in the complex genetics of Mullerian aplasia. Orphanet J Rare Dis 8:125

    Article  PubMed  PubMed Central  Google Scholar 

  • Sartori-Rupp A, Cordero Cervantes D, Pepe A, Gousset K, Delage E, Corroyer-Dulmont S, Schmitt C, Krijnse-Locker J, Zurzolo C (2019) Correlative cryo-electron microscopy reveals the structure of TNTs in neuronal cells. Nat Commun 10(1):342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sebe-Pedros A, Grau-Bove X, Richards TA, Ruiz-Trillo I (2014) Evolution and classification of myosins, a paneukaryotic whole-genome approach. Genome Biol Evol 6(2):290–305

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shneyer BI, Usaj M, Henn A (2016) Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia. J Cell Sci 129(3):543–556

    Article  CAS  PubMed  Google Scholar 

  • Shneyer BI, Usaj M, Wiesel-Motiuk N, Regev R, Henn A (2017) ROS induced distribution of mitochondria to filopodia by Myo19 depends on a class specific tryptophan in the motor domain. Sci Rep 7(1):11577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Smith CA, Rayment I (1996) Active site comparisons highlight structural similarities between myosin and other P-loop proteins. Biophys J 70(4):1590–1602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sousa AD, Berg JS, Robertson BW, Meeker RB, Cheney RE (2006) Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons. J Cell Sci 119(Pt 1):184–194

    Article  CAS  PubMed  Google Scholar 

  • Tsuiko O, Noukas M, Zilina O, Hensen K, Tapanainen JS, Magi R, Kals M, Kivistik PA, Haller-Kikkatalo K, Salumets A et al (2016) Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases. Hum Reprod 31(8):1913–1925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Usaj M, Henn A (2017) Kinetic adaptation of human Myo19 for active mitochondrial transport to growing filopodia tips. Sci Rep 7(1):11596

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wells AL, Lin AW, Chen LQ, Safer D, Cain SM, Hasson T, Carragher BO, Milligan RA, Sweeney HL (1999) Myosin VI is an actin-based motor that moves backwards. Nature 401(6752):505–508

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Chen X, Wei K, Liu D, Xu X, Zhang X, Shi H (2017) Identification of key transcription factors associated with lung squamous cell carcinoma. Med Sci Monit 23:172–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Myosin XIX studies by OAQ began as part of his NIH-IRACDA-funded postdoctoral fellowship with Richard Cheney at the University of North Carolina, Chapel Hill. OAQ is grateful to Richard Cheney and the greater cytoskeleton community at UNC. Additionally, the work was supported by The Franklin & Marshall College Department of Biology, The Whitman Summer Fellows Program at the MBL, Mount Holyoke College Department of Biology, and The Pennsylvania State University College of Medicine Department of Cellular & Molecular Physiology during OAQ’s appointments at each of those institutions. The studies were also supported by Ernest Everett Just Endowed Research Fellowship, Robert Day Allen Fellowship, and The Laura & Arthur Colwin Endowed Summer Research Fellowship from the MBL, as well as K01CA160667 & R15GM119077 from NIH. OAQ would like to thank Margaret Titus (University of Minnesota) and Christopher Yengo (Penn State College of Medicine) for their mentorship in the marvelous world of myosins, and the 60+ undergraduate researchers who have made discovery-based science a joy to share.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Omar A. Quintero .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bocanegra, J.L., Adikes, R., Quintero, O.A. (2020). Myosin XIX. In: Coluccio, L. (eds) Myosins. Advances in Experimental Medicine and Biology, vol 1239. Springer, Cham. https://doi.org/10.1007/978-3-030-38062-5_20

Download citation

Publish with us

Policies and ethics