Abstract
Rho GTPases including RhoA, Rac1, and Cdc42 are a class of intracellular signaling proteins critical for the regulation of cytoskeleton organization, adhesion, and migration. Molecular mechanisms of mammalian cell migration were first revealed in fibroblasts where RhoA, Rac1, and Cdc42 facilitate in the multistep process including establishment and maintenance of polarity, formation of actin-rich protrusions, remodeling of adhesive contacts, and generation of force. In hematopoietic stem/progenitor cells, Rho GTPases relay signals from chemokines and cytokines such as SDF-1α and SCF to the actin and microtubule cytoskeleton through effector kinases and/or adaptor molecules that affect adhesion or transcription. Comprehensive use of murine conditional gene knockout technology combined with biochemical approaches in recent studies allows for physiologically relevant investigations of the involvement of Rho GTPases in hematopoietic stem/progenitor cell migration, providing important mechanisms for the stem/progenitor maintenance.
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References
Hall, A. (1998) Rho GTPases and the actin cytoskeleton Science 279, 509–14.
Ridley, A.J., and Hall, A. (1998) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors Cell 70, 389–99.
Ridley, A.J. (2001) Rho GTPases and cell migration J Cell Sci 114, 2713–22.
Abo, A., Pick, E., Hall, A., Totty, N., Teahan, C.G., and Segal, A.W. (1991) Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1 Nature 353, 668–70.
Welsh, C.F., Roovers, K., Villanueva, J., Liu, Y., Schwartz, M.A., and Assoian, R.K. (2001) Timing of cyclin D1 expression within G1 phase is controlled by Rho Nat Cell Biol 3, 950–7.
Cantrell, D. (1998) Lymphocyte signalling: a coordinating role for Vav? Curr Biol 8, R535–8.
Sells, M.A., Pfaff, A., and Chernoff, J. (2000) Temporal and spatial distribution of activated Pak1 in fibroblasts J Cell Biol 151, 1449–58.
Etienne-Manneville, S., and Hall, A. (2001) Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta Cell 106, 489–98.
Nobes, C.D., and Hall, A. (1995) Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia Cell 81, 53–62.
Burridge, K., and Chrzanowska-Wodnicka, M. (1996) Focal adhesions, contractility, and signaling Annu Rev Cell Dev Biol 12, 463–518.
Rottner, K., Hall, A., and Small, J.V. (1999) Interplay between Rac and Rho in the control of substrate contact dynamics Curr Biol 9, 640–8.
Ren X.D., Kiosses W.B., and Schwartz M.A. (1999) Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J 18, 578–85.
Lapidot, T., Dar, A., and Kollet, O. (2005) How do stem cells find their way home? Blood 106, 1901–10.
Peled, A., Petit, I., Kollet, O., et al. (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4 Science 283, 845–8.
Peled, A., Kollet, O., Ponomaryov, T., et al. (2000) The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: role in transendothelial/stromal migration and engraftment of NOD/SCID mice Blood 95, 3289–96.
Whetton, A.D., Lu, Y., Pierce, A., Carney, L., and Spooncer, E. (2003) Lysophospholipids synergistically promote primitive hematopoietic cell chemotaxis via a mechanism involving Vav 1 Blood 102, 2798–802.
Yang, F.C., Atkinson, S.J., Gu, Y., et al. (2001) Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization Proc Natl Acad Sci USA 98, 5614–8.
Gu, Y., Filippi, M.D., Cancelas, J.A., et al. (2003) Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases Science 302, 445–9.
Yang, L., Wang, L., Geiger, H., Cancelas, J.A., Mo, J., and Zheng, Y. (2007) Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow Proc Natl Acad Sci USA 104, 5091–6.
Benard, V., Bohl, B.P., and Bokoch, G.M. (1999) Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases J Biol Chem 274, 13198–204.
Levesque, J.P., Leavesley, D.I., Niutta, S., Vadas, M., and Simmons, P.J. (1995) Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins J Exp Med 181, 1805–15.
Ridley, A.J., Schwartz, M.A., Burridge, K., et al. (2003) Cell migration: integrating signals from front to back Science 302, 1704–09.
Mohle, R., Moore, M.A., Nachman, R.L., and Rafii, S. (1997) Transendothelial migration of CD34+ and mature hematopoietic cells: an in vitro study using a human bone marrow endothelial cell line Blood 89, 72–80.
Yong, K.L., Watts, M., Shaun Thomas, N., Sullivan, A., Ings, S., and Linch, D.C. (1998) Transmigration of CD34+ cells across specialized and nonspecialized endothelium requires prior activation by growth factors and is mediated by PECAM-1 (CD31) Blood 91, 1196–205.
Imai, K., Kobayashi, M., Wang, J., et al. (1999) Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells Blood 93, 149–56.
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Liu, W., Feng, Y., Shang, X., Zheng, Y. (2011). Rho GTPases in Hematopoietic Stem/Progenitor Cell Migration. In: Filippi, MD., Geiger, H. (eds) Stem Cell Migration. Methods in Molecular Biology, vol 750. Humana Press. https://doi.org/10.1007/978-1-61779-145-1_21
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DOI: https://doi.org/10.1007/978-1-61779-145-1_21
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