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Migration of Stem Cells: Role of the RhoA/ROCK I Pathway (Method)

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Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 6))

Abstract

Cell migration is an important biological phenomenon that has come under the spotlight following the worldwide emergence of stem cell-based therapies. How a given stem cell migrates within an organism to reach its final destination, known as the stem cell niche, to replenish a cellular system is a question of interest. The development of new cell-isolation and transfection techniques together with ex vivo culture systems have allowed the successful isolation, manipulation and expansion of stem cells. When combined with real-time imaging techniques, novel biochemical tools such as RNA interference oligonucleotides and animal models, have shed new light on the mechanisms that regulate stem cell migration. Here, we summarize the migration mechanisms that are based on biochemical pathways related to Rho GTPases. In particular, we focus on the RhoA/ROCK I pathway that affects the polarization of hematopoietic stem and progenitor cells and therefore the driving forces underlying migration.

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References

  • Aktories K (2011) Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol 9:487–498

    Article  PubMed  CAS  Google Scholar 

  • Amano M, Fukata Y, Kaibuchi K (2000) Regulation and functions of Rho-associated kinase. Exp Cell Res 261:44–51

    Article  PubMed  CAS  Google Scholar 

  • Amano M, Tsumura Y, Taki K, Harada H, Mori K, Nishioka T, Kato K, Suzuki T, Nishioka Y, Iwamatsu A, Kaibuchi K (2010) A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase. PLoS One 5:e8704

    Article  PubMed  Google Scholar 

  • Bauer N, Fonseca AV, Florek M, Freund D, Jászai J, Bornhäuser M, Fargeas CA, Corbeil D (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cell Tissue Organs 188:127–138

    Article  CAS  Google Scholar 

  • Bauer N, Wilsch-Bräuninger M, Karbanová J, Fonseca AV, Strauss D, Freund D, Thiele C, Huttner WB, Bornhäuser M, Corbeil D (2011) Hematopoietic stem cell differentiation promotes the release of prominin-1/CD133–containing membrane vesicles – a role of the endocytic-exocytic pathway. EMBO Mol Med 3:398–409

    Article  PubMed  CAS  Google Scholar 

  • Benard V, Bokoch GM (2002) Assay of Cdc42, Rac, and Rho GTPase activation by affinity methods. Methods Enzymol 345:349–359

    Article  PubMed  Google Scholar 

  • Chang YC, Nalbant P, Birkenfeld J, Chang ZF, Bokoch GM (2008) GEF-H1 couples nocodazole-induced microtubule disassembly to cell contractility via RhoA. Mol Biol Cell 19:2147–2153

    Article  PubMed  CAS  Google Scholar 

  • Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208:421–428

    Article  PubMed  CAS  Google Scholar 

  • Etienne-Manneville S (2004) Actin and microtubules in cell motility: which one is in control? Traffic 5:470–477

    Article  PubMed  CAS  Google Scholar 

  • Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420:629–635

    Article  PubMed  CAS  Google Scholar 

  • Fonseca AV, Corbeil D (2011) The hematopoietic stem cell polarization and migration: a dynamic link between RhoA signaling pathway, microtubule network and ganglioside-based membrane microdomains. Commun Integr Biol 4:201–204

    Article  PubMed  CAS  Google Scholar 

  • Fonseca AV, Bauer N, Corbeil D (2008) The stem cell marker CD133 meets the endosomal compartment – new insights into the cell division of hematopoietic stem cells. Blood Cells Mol Dis 41:194–195

    Article  PubMed  CAS  Google Scholar 

  • Fonseca AV, Freund D, Bornhäuser M, Corbeil D (2010) Polarization and migration of hematopoietic stem and progenitor cells rely on the RhoA/ROCK I pathway and an active reorganization of the microtubule network. J Biol Chem 285:31661–31671

    Article  PubMed  CAS  Google Scholar 

  • Freund D, Bauer N, Boxberger S, Feldmann S, Streller U, Ehninger G, Werner C, Bornhäuser M, Oswald J, Corbeil D (2006a) Polarization of human hematopoietic progenitors during contact with multipotent mesenchymal stromal cells: effects on proliferation and clonogenicity. Stem Cells Dev 15:815–829

    Article  PubMed  CAS  Google Scholar 

  • Freund D, Oswald J, Feldmann S, Ehninger G, Corbeil D, Bornhäuser M (2006b) Comparative analysis of proliferative potential and clonogenicity of MACS-immunomagnetic isolated CD34+ and CD133+ blood stem cells derived from a single donor. Cell Prolif 39:325–332

    Article  PubMed  CAS  Google Scholar 

  • Ghiaur G, Lee A, Bailey J, Cancelas JA, Zheng Y, Williams DA (2006) Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment. Blood 108:2087–2094

    Article  PubMed  CAS  Google Scholar 

  • Giebel B, Corbeil D, Beckmann J, Hohn J, Freund D, Giesen K, Fischer J, Kogler G, Wernet P (2004) Segregation of lipid raft markers including CD133 in polarized human hematopoietic stem and progenitor cells. Blood 104:2332–2338

    Article  PubMed  CAS  Google Scholar 

  • Gillette JM, Larochelle A, Dunbar CE, Lippincott-Schwartz J (2009) Intercellular transfer to signalling endosomes regulates an ex vivo bone marrow niche. Nat Cell Biol 11:303–311

    Article  PubMed  CAS  Google Scholar 

  • Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269

    Article  PubMed  CAS  Google Scholar 

  • Jing D, Fonseca AV, Alakel N, Fierro FA, Muller K, Bornhäuser M, Ehninger G, Corbeil D, Ordemann R (2010) Hematopoietic stem cells in co-culture with mesenchymal stromal cells–modeling the niche compartments in vitro. Haematologica 95:542–550

    Article  PubMed  CAS  Google Scholar 

  • Kawano Y, Fukata Y, Oshiro N, Amano M, Nakamura T, Ito M, Matsumura F, Inagaki M, Kaibuchi K (1999) Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo. J Cell Biol 147:1023–1038

    Article  PubMed  CAS  Google Scholar 

  • Lapid K, Vagima Y, Kollet O, Lapidot T (2008–2009) Egress and mobilization of hematopoietic stem and progenitor cells. StemBook [Internet]. Harvard Stem Cell Institute, Cambridge. PMID: 20614623

    Google Scholar 

  • Lee JH, Katakai T, Hara T, Gonda H, Sugai M, Shimizu A (2004) Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation. J Cell Biol 167:327–337

    Article  PubMed  CAS  Google Scholar 

  • Liu W, Feng Y, Shang X, Zheng Y (2011) Rho GTPases in hematopoietic stem/progenitor cell migration. Methods Mol Biol 750:307–319

    Article  PubMed  Google Scholar 

  • Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S (1999) Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285:895–898

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y, Shibata H, Nakano T (2000) In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells 18:196–203

    Article  PubMed  CAS  Google Scholar 

  • Miltenyi S, Müller W, Weichel W, Radbruch A (1990) High gradient magnetic cell separation with MACS. Cytometry 11:231–238

    Article  PubMed  CAS  Google Scholar 

  • Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90:5013–5021

    PubMed  CAS  Google Scholar 

  • Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S (1996) ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Lett 392:189–193

    Article  PubMed  CAS  Google Scholar 

  • Niehage C, Steenblock C, Pursche T, Bornhäuser M, Corbeil D, Hoflack B (2011) The cell surface proteome of human mesenchymal stromal cells. PLoS One 6:e20399

    Article  PubMed  CAS  Google Scholar 

  • Palazzo AF, Joseph HL, Chen YJ, Dujardin DL, Alberts AS, Pfister KK, Vallee RB, Gundersen GG (2001) Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Curr Biol 11:1536–1541

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ (2011) Life at the leading edge. Cell 145:1012–1022

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70:401–410

    Article  PubMed  CAS  Google Scholar 

  • Riento K, Ridley AJ (2003) ROCKS: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4:446–456

    Article  PubMed  CAS  Google Scholar 

  • Sánchez-Madrid F, Serrador JM (2009) Bringing up the rear: defining the roles of the uropod. Nat Rev Mol Cell Biol 10:353–359

    Article  PubMed  Google Scholar 

  • Smith A, Bracke M, Leitinger B, Porter JC, Hogg N (2003) LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment. J Cell Sci 116:3123–3133

    Article  PubMed  CAS  Google Scholar 

  • Torrente Y, Belicchi M, Marchesi C, Dantona G, Cogiamanian F, Pisati F, Gavina M, Giordano R, Tonlorenzi R, Fagiolari G, Lamperti C, Porretti L, Lopa R, Sampaolesi M, Vicentini L, Grimoldi N, Tiberio F, Songa V, Baratta P, Prelle A, Forzenigo L, Guglieri M, Pansarasa O, Rinaldi C, Mouly V, Butler-Browne GS, Comi GP, Biondetti P, Moggio M, Gaini SM, Stocchetti N, Priori A, D’Angelo MG, Turconi A, Bottinelli R, Cossu G, Rebulla P, Bresolin N (2007) Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Cell Transplant 16:563–577

    PubMed  CAS  Google Scholar 

  • von Levetzow G, Spanholtz J, Beckmann J, Fischer J, Kögler G, Wernet P, Punzel M, Giebel B (2006) Nucleofection, an efficient nonviral method to transfer genes into human hematopoietic stem and progenitor cells. Stem Cells Dev 15:278–285

    Article  Google Scholar 

  • Webb DJ, Parsons JT, Horwitz AF (2002) Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again. Nat Cell Biol 4:E97–E100

    Article  PubMed  CAS  Google Scholar 

  • Williams DA, Zheng Y, Cancelas JA (2008) Rho GTPases and regulation of hematopoietic stem cell localization. Methods Enzymol 439:365–393

    Article  PubMed  CAS  Google Scholar 

  • Wittmann T, Waterman-Storer CM (2001) Cell motility: can Rho GTPases and microtubules point the way? J Cell Sci 114:3795–3803

    PubMed  CAS  Google Scholar 

  • Worthylake RA, Burridge K (2001) Leukocyte transendothelial migration: orchestrating the underlying molecular machinery. Curr Opin Cell Biol 13:569–577

    Article  PubMed  CAS  Google Scholar 

  • Worthylake RA, Burridge K (2003) RhoA and ROCK promote migration by limiting membrane protrusions. J Biol Chem 278:13578–13584

    Article  PubMed  CAS  Google Scholar 

  • Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012

    PubMed  CAS  Google Scholar 

  • Yoneda A, Multhaupt HA, Couchman JR (2005) The Rho kinases I and II regulate different aspects of myosin II activity. J Cell Biol 170:443–453

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

The study was supported by Deutsche Forschungsgemeinschaft (TRR83 No. 6, SFB655 B3 and CO298/5-1).

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Correspondence to Denis Corbeil .

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Fonseca, AV., Reichert, D., Corbeil, D. (2012). Migration of Stem Cells: Role of the RhoA/ROCK I Pathway (Method). In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 6. Stem Cells and Cancer Stem Cells, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2993-3_28

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