Abstract
Cell movement involves a coordinated regulation of the cytoskeleton, F-actin-mediated protrusions at the front and myosin-mediated contraction of the posterior of a cell. The small GTPase Rap1 functions as a key regulator in the spatial and temporal control of cytoskeleton reorganization for cell migration. This review outlines the establishment of cell polarity by differential localizations of the cytoskeleton and discusses the spatial and temporal regulation of cytoskeleton reorganization via the Rap1 signaling pathway during chemotaxis with a focus on recent advances in the study of chemotaxis using a simple eukaryotic model organism, Dictyostelium discoideum.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Arthur, W.T., Quilliam, L.A., and Cooper, J.A. 2004. Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J. Cell Biol. 167, 111–122.
Bosgraaf, L. and van Haastert, P.J. 2006. The regulation of myosin II in Dictyostelium. Eur. J. Cell Biol. 85, 969–979.
Bosgraaf, L., Waijer, A., Engel, R., Visser, A.J., Wessels, D., Soll, D., and van Haastert, P.J. 2005. RasGEF-containing proteins GbpC and GbpD have differential effects on cell polarity and chemotaxis in Dictyostelium. J. Cell Sci. 118, 1899–1910.
Cha, I. and Jeon, T.J. 2011. Dynamic localization of the actin-bundling protein cortexillin I during cell migration. Mol. Cells 32, 281–287.
Cha, I., Lee, S.H., and Jeon, T.J. 2010. Chemoattractant-mediated Rap1 activation requires GPCR/G proteins. Mol. Cells 30, 563–567.
Chisholm, R.L. and Firtel, R.A. 2004. Insights into morphogenesis from a simple developmental system. Nat. Rev. Mol. Cell Biol. 5, 531–541.
Chung, C.Y., Funamoto, S., and Firtel, R.A. 2001. Signaling pathways controlling cell polarity and chemotaxis. Trends Biochem. Sci. 26, 557–566.
De Lozanne, A. and Spudich, J.A. 1987. Disruption of the Dictyostelium myosin heavy chain gene by homologous recombination. Science 236, 1086–1091.
Firat-Karalar, E.N. and Welch, M.D. 2011. New mechanisms and functions of actin nucleation. Curr. Opin. Cell Biol. 23, 4–13.
Gebbie, L., Benghezal, M., Cornillon, S., Froquet, R., Cherix, N., Malbouyres, M., Lefkir, Y., Grangeasse, C., Fache, S., Dalous, J., and et al. 2004. Phg2, a kinase involved in adhesion and focal site modeling in Dictyostelium. Mol. Biol. Cell. 15, 3915–3925.
Glading, A., Han, J., Stockton, R.A., and Ginsberg, M.H. 2007. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J. Cell Biol. 179, 247–254.
Goldberg, J.M., Bosgraaf, L., Van Haastert, P.J., and Smith, J.L. 2002. Identification of four candidate cGMP targets in Dictyostelium. Proc. Natl. Acad. Sci. USA 99, 6749–6754.
Hoshino, T., Sakisaka, T., Baba, T., Yamada, T., Kimura, T., and Takai, Y. 2005. Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn. J. Biol. Chem. 280, 24095–24103.
Jeon, T.J., Lee, D.J., Lee, S., Weeks, G., and Firtel, R.A. 2007a. Regulation of Rap1 activity by RapGAP1 controls cell adhesion at the front of chemotaxing cells. J. Cell Biol. 179, 833–843.
Jeon, T.J., Lee, D.J., Merlot, S., Weeks, G., and Firtel, R.A. 2007b. Rap1 controls cell adhesion and cell motility through the regulation of myosin II. J. Cell Biol. 176, 1021–1033.
Jeon, T.J., Lee, S., Weeks, G., and Firtel, R.A. 2009. Regulation of Dictyostelium morphogenesis by RapGAP3. Dev. Biol. 328, 210–220.
Jin, T., Xu, X., Fang, J., Isik, N., Yan, J., Brzostowski, J.A., and Hereld, D. 2009. How human leukocytes track down and destroy pathogens: lessons learned from the model organism Dictyostelium discoideum. Immunol. Res. 43, 118–127.
Jin, T., Xu, X., and Hereld, D. 2008. Chemotaxis, chemokine receptors and human disease. Cytokine 44, 1–8.
Katagiri, K., Imamura, M., and Kinashi, T. 2006. Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nat. Immunol. 7, 919–928.
Kolsch, V., Charest, P.G., and Firtel, R.A. 2008. The regulation of cell motility and chemotaxis by phospholipid signaling. J. Cell Sci. 121, 551–559.
Kooistra, M.R., Dube, N., and Bos, J.L. 2007. Rap1: a key regulator in cell-cell junction formation. J. Cell Sci. 120, 17–22.
Kortholt, A., Rehmann, H., Kae, H., Bosgraaf, L., Keizer-Gunnink, I., Weeks, G., Wittinghofer, A., and Van Haastert, P.J. 2006. Characterization of the GbpD-activated Rap1 pathway regulating adhesion and cell polarity in Dictyostelium discoideum. J. Biol. Chem. 281, 23367–23376.
Kortholt, A. and van Haastert, P.J. 2008. Highlighting the role of Ras and Rap during Dictyostelium chemotaxis. Cell Signal 20, 1415–1422.
Krause, M., Leslie, J.D., Stewart, M., Lafuente, E.M., Valderrama, F., Jagannathan, R., Strasser, G.A., Rubinson, D.A., Liu, H., Way, M., and et al. 2004. Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Dev. Cell 7, 571–583.
Krugmann, S., Andrews, S., Stephens, L., and Hawkins, P.T. 2006. ARAP3 is essential for formation of lamellipodia after growth factor stimulation. J. Cell Sci. 119, 425–432.
Lee, H.S., Lim, C.J., Puzon-McLaughlin, W., Shattil, S.J., and Ginsberg, M.H. 2009. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J. Biol. Chem. 284, 5119–5127.
Lee, S., Shen, Z., Robinson, D.N., Briggs, S., and Firtel, R.A. 2010. Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis. Mol. Biol. Cell 21, 1810–1824.
Medeiros, R.B., Dickey, D.M., Chung, H., Quale, A.C., Nagarajan, L.R., Billadeau, D.D., and Shimizu, Y. 2005. Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1 integrin function via regulation of Rap1 activation. Immunity 23, 213–226.
Meili, R., Alonso-Latorre, B., del Alamo, J.C., Firtel, R.A., and Lasheras, J.C. 2010. Myosin II is essential for the spatiotemporal organization of traction forces during cell motility. Mol. Biol. Cell 21, 405–417.
Mun, H. and Jeon, T.J. 2012. Regulation of actin cytoskeleton by Rap1 binding to RacGEF1. Mol. Cells DOI/10.1007/s10059-012-0097-Z.
Parkinson, K., Bolourani, P., Traynor, D., Aldren, N.L., Kay, R.R., Weeks, G., and Thompson, C.R. 2009. Regulation of Rap1 activity is required for differential adhesion, cell-type patterning and morphogenesis in Dictyostelium. J. Cell Sci. 122, 335–344.
Pasternak, C., Spudich, J.A., and Elson, E.L. 1989. Capping of surface receptors and concomitant cortical tension are generated by conventional myosin. Nature 341, 549–551.
Raaijmakers, J.H. and Bos, J.L. 2009. Specificity in Ras and Rap signaling. J. Biol. Chem. 284, 10995–10999.
Ridley, A.J., Schwartz, M.A., Burridge, K., Firtel, R.A., Ginsberg, M.H., Borisy, G., Parsons, J.T., and Horwitz, A.R. 2003. Cell migration: integrating signals from front to back. Science 302, 1704–1709.
Rodal, A.A., Sokolova, O., Robins, D.B., Daugherty, K.M., Hippenmeyer, S., Riezman, H., Grigorieff, N., and Goode, B.L. 2005. Conformational changes in the Arp2/3 complex leading to actin nucleation. Nat. Struct. Mol. Biol. 12, 26–31.
Sasaki, A.T., Chun, C., Takeda, K., and Firtel, R.A. 2004. Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement. J. Cell Biol. 167, 505–518.
Steimle, P.A., Yumura, S., Cote, G.P., Medley, Q.G., Polyakov, M.V., Leppert, B., and Egelhoff, T.T. 2001. Recruitment of a myosin heavy chain kinase to actin-rich protrusions in Dictyostelium. Curr. Biol. 11, 708–713.
Stephens, L., Milne, L., and Hawkins, P. 2008. Moving towards a better understanding of chemotaxis. Curr. Biol. 18, R485–494.
Wilkins, A., Szafranski, K., Fraser, D.J., Bakthavatsalam, D., Muller, R., Fisher, P.R., Glockner, G., Eichinger, L., Noegel, A.A., and Insall, R.H. 2005. The Dictyostelium genome encodes numerous RasGEFs with multiple biological roles. Genome Biol. 6, R68.
Williams, R.S., Boeckeler, K., Graf, R., Muller-Taubenberger, A., Li, Z., Isberg, R.R., Wessels, D., Soll, D.R., Alexander, H., and Alexander, S. 2006. Towards a molecular understanding of human diseases using Dictyostelium discoideum. Trends Mol. Med. 12, 415–424.
Worthylake, R.A. and Burridge, K. 2003. RhoA and ROCK promote migration by limiting membrane protrusions. J. Biol. Chem. 278, 13578–13584.
Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K., Takuwa, Y., Sugimoto, N., Mitchison, T., and Bourne, H.R. 2003. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114, 201–214.
Yamada, T., Sakisaka, T., Hisata, S., Baba, T., and Takai, Y. 2005. RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. J. Biol. Chem. 280, 33026–33034.
Yumura, S., Yoshida, M., Betapudi, V., Licate, L.S., Iwadate, Y., Nagasaki, A., Uyeda, T.Q., and Egelhoff, T.T. 2005. Multiple myosin II heavy chain kinases: roles in filament assembly control and proper cytokinesis in Dictyostelium. Mol. Biol. Cell 16, 4256–4266.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, MR., Jeon, T.J. Cell Migration: Regulation of cytoskeleton by Rap1 in Dictyostelium discoideum . J Microbiol. 50, 555–561 (2012). https://doi.org/10.1007/s12275-012-2246-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12275-012-2246-7