Crosstalk between small GTPases and polarity proteins in cell polarization (original) (raw)
Goldstein, B. & Macara, I. G. The PAR proteins: fundamental players in animal cell polarization. Dev. Cell13, 609–622 (2007). Excellent review on the discovery of thePARgenes and the various functions of PAR proteins in different species and cell types. CASPubMedPubMed Central Google Scholar
Assemat, E., Bazellieres, E., Pallesi-Pocachard, E., Le Bivic, A. & Massey-Harroche, D. Polarity complex proteins. Biochim. Biophys. Acta1778, 614–630 (2008). CASPubMed Google Scholar
Humbert, P. O., Dow, L. E. & Russell, S. M. The Scribble and Par complexes in polarity and migration: friends or foes? Trends Cell Biol.16, 622–630 (2006). CASPubMed Google Scholar
Bos, J. L. Linking Rap to cell adhesion. Curr. Opin. Cell Biol.17, 123–128 (2005). CASPubMed Google Scholar
Jaffe, A. B. & Hall, A. Rho GTPases: biochemistry and biology. Annu. Rev. Cell Dev. Biol.21, 247–269 (2005). CASPubMed Google Scholar
Nobes, C. D. & Hall, A. Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell81, 53–62 (1995). CASPubMed Google Scholar
Sander, E. E., ten Klooster, J. P., van Delft, S., van der Kammen, R. A. & Collard, J. G. Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J. Cell Biol.147, 1009–1022 (1999). CASPubMedPubMed Central Google Scholar
Nimnual, A. S., Taylor, L. J. & Bar-Sagi, D. Redox-dependent downregulation of Rho by Rac. Nature Cell Biol.5, 236–241 (2003). CASPubMed Google Scholar
Knoblich, J. A. Mechanisms of asymmetric stem cell division. Cell132, 583–597 (2008). CASPubMed Google Scholar
Gonczy, P. Mechanisms of asymmetric cell division: flies and worms pave the way. Nature Rev. Mol. Cell Biol.9, 355–366 (2008). Google Scholar
Kemphues, K. J., Priess, J. R., Morton, D. G. & Cheng, N. S. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell52, 311–320 (1988). CASPubMed Google Scholar
Watts, J. L. et al. par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. Development122, 3133–3140 (1996). CASPubMed Google Scholar
Cowan, C. R. & Hyman, A. A. Acto-myosin reorganization and PAR polarity in C. elegans. Development134, 1035–1043 (2007). CASPubMed Google Scholar
Schonegg, S., Constantinescu, A. T., Hoege, C. & Hyman, A. A. The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos. Proc. Natl Acad. Sci. USA104, 14976–14981 (2007). CASPubMedPubMed Central Google Scholar
Albertson, R. & Doe, C. Q. Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nature Cell Biol.5, 166–170 (2003). CASPubMed Google Scholar
Betschinger, J. & Knoblich, J. A. Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Curr. Biol.14, R674–R685 (2004). CASPubMed Google Scholar
Peng, C. Y., Manning, L., Albertson, R. & Doe, C. Q. The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature408, 596–600 (2000). CASPubMed Google Scholar
Ohshiro, T., Yagami, T., Zhang, C. & Matsuzaki, F. Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature408, 593–596 (2000). CASPubMed Google Scholar
Betschinger, J., Mechtler, K. & Knoblich, J. A. The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature422, 326–330 (2003). CASPubMed Google Scholar
Duncan, F. E., Moss, S. B., Schultz, R. M. & Williams, C. J. PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs. Dev. Biol.280, 38–47 (2005). CASPubMed Google Scholar
Vinot, S. et al. Asymmetric distribution of PAR proteins in the mouse embryo begins at the 8-cell stage during compaction. Dev. Biol.282, 307–319 (2005). CASPubMed Google Scholar
Costa, M. R., Wen, G., Lepier, A., Schroeder, T. & Gotz, M. Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex. Development135, 11–22 (2008). CASPubMed Google Scholar
Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature437, 275–280 (2005). CASPubMedPubMed Central Google Scholar
Chang, J. T. et al. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science315, 1687–1691 (2007). CASPubMed Google Scholar
Watabe-Uchida, M., Govek, E. E. & Van Aelst, L. Regulators of Rho GTPases in neuronal development. J. Neurosci.26, 10633–10635 (2006). CASPubMedPubMed Central Google Scholar
Arimura, N. & Kaibuchi, K. Neuronal polarity: from extracellular signals to intracellular mechanisms. Nature Rev. Neurosci.8, 194–205 (2007). CAS Google Scholar
Kozma, R., Sarner, S., Ahmed, S. & Lim, L. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol. Cell. Biol.17, 1201–1211 (1997). CASPubMedPubMed Central Google Scholar
van Leeuwen, F. N., van Delft, S., Kain, H. E., van der Kammen, R. A. & Collard, J. G. Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading. Nature Cell. Biol.1, 242–248 (1999). CASPubMed Google Scholar
Schwamborn, J. C. & Puschel, A. W. The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nature Neurosci.7, 923–929 (2004). CASPubMed Google Scholar
Kunda, P., Paglini, G., Quiroga, S., Kosik, K. & Caceres, A. Evidence for the involvement of Tiam1 in axon formation. J. Neurosci.21, 2361–2372 (2001). CASPubMedPubMed Central Google Scholar
Curmi, P. A. et al. Stathmin and its phosphoprotein family: general properties, biochemical and functional interaction with tubulin. Cell Struct. Funct.24, 345–357 (1999). CASPubMed Google Scholar
Witte, H., Neukirchen, D. & Bradke, F. Microtubule stabilization specifies initial neuronal polarization. J. Cell Biol.180, 619–632 (2008). CASPubMedPubMed Central Google Scholar
Nishimura, T. et al. PAR-6–PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature Cell Biol.7, 270–277 (2005). This work, together with that of reference 29, unravelled a signalling pathway that involves RAP1, CDC42, RAC1 and crosstalk of these GTPases to PAR polarity proteins during axonal specification. CASPubMed Google Scholar
Schwamborn, J. C., Muller, M., Becker, A. H. & Puschel, A. W. Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. EMBO J.26, 1410–1422 (2007). CASPubMedPubMed Central Google Scholar
Nishimura, T. et al. Role of the PAR-3–KIF3 complex in the establishment of neuronal polarity. Nature Cell Biol.6, 328–334 (2004). CASPubMed Google Scholar
Schwamborn, J. C., Khazaei, M. R. & Puschel, A. W. The interaction of mPar3 with the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. J. Biol. Chem.282, 35259–35268 (2007). CASPubMed Google Scholar
Wang, H. R. et al. Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science302, 1775–1779 (2003). CASPubMed Google Scholar
Fivaz, M., Bandara, S., Inoue, T. & Meyer, T. Robust neuronal symmetry breaking by Ras-triggered local positive feedback. Curr. Biol.18, 44–50 (2008). CASPubMed Google Scholar
Oinuma, I., Katoh, H. & Negishi, M. R. Ras controls axon specification upstream of glycogen synthase kinase-3β through integrin-linked kinase. J. Biol. Chem.282, 303–318 (2007). CASPubMed Google Scholar
Shi, S. H., Jan, L. Y. & Jan, Y. N. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell112, 63–75 (2003). CASPubMed Google Scholar
Tashiro, A., Minden, A. & Yuste, R. Regulation of dendritic spine morphology by the Rho family of small GTPases: antagonistic roles of Rac and Rho. Cereb Cortex.10, 927–938 (2000). CASPubMed Google Scholar
Tashiro, A. & Yuste, R. Role of Rho GTPases in the morphogenesis and motility of dendritic spines. Methods Enzymol.439, 285–302 (2008). CASPubMed Google Scholar
Zhang, H. & Macara, I. G. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nature Cell Biol.8, 227–237 (2006). CASPubMed Google Scholar
Zhang, H. & Macara, I. G. The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Dev. Cell14, 216–226 (2008). Shows that the PAR6–aPKC-mediated downregulation of RhoA involves p190 RhoGAP in the formation of dendritic spines. PubMedPubMed Central Google Scholar
Xie, Z., Huganir, R. L. & Penzes, P. Activity-dependent dendritic spine structural plasticity is regulated by small GTPase Rap1 and its target AF-6. Neuron48, 605–618 (2005). CASPubMed Google Scholar
Pak, D. T., Yang, S., Rudolph-Correia, S., Kim, E. & Sheng, M. Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP. Neuron31, 289–303 (2001). CASPubMed Google Scholar
del Pozo, M. A. et al. ICAMs redistributed by chemokines to cellular uropods as a mechanism for recruitment of T lymphocytes. J. Cell Biol.137, 493–508 (1997). CASPubMedPubMed Central Google Scholar
Krummel, M. F. & Macara, I. Maintenance and modulation of T cell polarity. Nature Immunol.7, 1143–1149 (2006). CAS Google Scholar
del Pozo, M. A., Vicente-Manzanares, M., Tejedor, R., Serrador, J. M. & Sanchez-Madrid, F. Rho GTPases control migration and polarization of adhesion molecules and cytoskeletal ERM components in T lymphocytes. Eur. J. Immunol.29, 3609–3620 (1999). CASPubMed Google Scholar
D'Souza-Schorey, C., Boettner, B. & Van Aelst, L. Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes. Mol. Cell. Biol.18, 3936–3946 (1998). CASPubMedPubMed Central Google Scholar
Nurmi, S. M., Autero, M., Raunio, A. K., Gahmberg, C. G. & Fagerholm, S. C. Phosphorylation of the LFA-1 integrin β2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation, and stimulation of CD69 expression in human T cells. J. Biol. Chem.282, 968–975 (2007). CASPubMed Google Scholar
Lee, J. H. et al. Roles of p-ERM and Rho–ROCK signaling in lymphocyte polarity and uropod formation. J. Cell Biol.167, 327–337 (2004). CASPubMedPubMed Central Google Scholar
Shimonaka, M. et al. Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J. Cell Biol.161, 417–427 (2003). CASPubMedPubMed Central Google Scholar
Gerard, A., Mertens, A. E., van der Kammen, R. A. & Collard, J. G. The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization. J. Cell Biol.176, 863–875 (2007). CASPubMedPubMed Central Google Scholar
Ludford-Menting, M. J. et al. A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation. Immunity22, 737–748 (2005). CASPubMed Google Scholar
Labno, C. M. et al. Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Curr. Biol.13, 1619–1624 (2003). CASPubMedPubMed Central Google Scholar
Faure, S. et al. ERM proteins regulate cytoskeleton relaxation promoting T cell–APC conjugation. Nature Immunol.5, 272–279 (2004). CAS Google Scholar
Yeh, J. H., Sidhu, S. S. & Chan, A. C. Regulation of a late phase of T cell polarity and effector functions by Crtam. Cell132, 846–859 (2008). CASPubMed Google Scholar
Yamada, S. & Nelson, W. J. Synapses: sites of cell recognition, adhesion, and functional specification. Annu. Rev. Biochem.76, 267–294 (2007). CASPubMedPubMed Central Google Scholar
Yamanaka, T. & Ohno, S. Role of Lgl/Dlg/Scribble in the regulation of epithelial junction, polarity and growth. Front. Biosci.13, 6693–6707 (2008). CASPubMed Google Scholar
Gumbiner, B. & Simons, K. The role of uvomorulin in the formation of epithelial occluding junctions. Ciba Found. Symp.125, 168–186 (1987). CASPubMed Google Scholar
Nakagawa, M., Fukata, M., Yamaga, M., Itoh, N. & Kaibuchi, K. Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell–cell adhesion sites. J. Cell Sci.114, 1829–1838 (2001). CASPubMed Google Scholar
Kim, S. H., Li, Z. & Sacks, D. B. E-cadherin-mediated cell–cell attachment activates Cdc42. J. Biol. Chem.275, 36999–37005 (2000). CASPubMed Google Scholar
Fukuhara, T. et al. Activation of Cdc42 by trans interactions of the cell adhesion molecules nectins through c-Src and Cdc42–GEF FRG. J. Cell Biol.166, 393–405 (2004). CASPubMedPubMed Central Google Scholar
Kawakatsu, T. et al. _Trans_-interactions of nectins induce formation of filopodia and Lamellipodia through the respective activation of Cdc42 and Rac small G proteins. J. Biol. Chem.277, 50749–50755 (2002). CASPubMed Google Scholar
Yamanaka, T. et al. PAR-6 regulates aPKC activity in a novel way and mediates cell–cell contact-induced formation of the epithelial junctional complex. Genes Cells6, 721–731 (2001). Proposes a mechanism through which binding of CDC42 to PAR6 might lead to aPKC activation, which is a crucial event in several polarization processes. CASPubMed Google Scholar
Takaishi, K., Sasaki, T., Kotani, H., Nishioka, H. & Takai, Y. Regulation of cell–cell adhesion by rac and rho small G proteins in MDCK cells. J. Cell Biol.139, 1047–1059 (1997). CASPubMedPubMed Central Google Scholar
Chen, X. & Macara, I. G. Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nature Cell Biol.7, 262–269 (2005). CASPubMed Google Scholar
Mertens, A. E., Rygiel, T. P., Olivo, C., van der Kammen, R. & Collard, J. G. The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex. J. Cell Biol.170, 1029–1037 (2005). References 69 and 70 show that TIAM1, in association with PAR3, controls tight-junction biogenesis in epithelial cells. CASPubMedPubMed Central Google Scholar
O'Brien, L. E. et al. Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nature Cell Biol.3, 831–838 (2001). CASPubMed Google Scholar
Liu, K. D. et al. Rac1 is required for reorientation of polarity and lumen formation through a PI 3-kinase-dependent pathway. Am. J. Physiol. Renal Physiol.293, F1633–F1640 (2007). CASPubMed Google Scholar
Mertens, A. E., Pegtel, D. M. & Collard, J. G. Tiam1 takes PARt in cell polarity. Trends Cell Biol.16, 308–316 (2006). CASPubMed Google Scholar
Martin-Belmonte, F. et al. Cell-polarity dynamics controls the mechanism of lumen formation in epithelial morphogenesis. Curr. Biol.18, 507–513 (2008). CASPubMedPubMed Central Google Scholar
Noren, N. K., Niessen, C. M., Gumbiner, B. M. & Burridge, K. Cadherin engagement regulates Rho family GTPases. J. Biol. Chem.276, 33305–33308 (2001). CASPubMed Google Scholar
Wildenberg, G. A. et al. p120-catenin and p190RhoGAP regulate cell–cell adhesion by coordinating antagonism between Rac and Rho. Cell127, 1027–1039 (2006). CASPubMed Google Scholar
Yamada, S. & Nelson, W. J. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell–cell adhesion. J. Cell Biol.178, 517–527 (2007). CASPubMedPubMed Central Google Scholar
Ivanov, A. I., Hunt, D., Utech, M., Nusrat, A. & Parkos, C. A. Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex. Mol. Biol. Cell16, 2636–2650 (2005). CASPubMedPubMed Central Google Scholar
Vaezi, A., Bauer, C., Vasioukhin, V. & Fuchs, E. Actin cable dynamics and Rho/Rock orchestrate a polarized cytoskeletal architecture in the early steps of assembling a stratified epithelium. Dev. Cell3, 367–381 (2002). CASPubMed Google Scholar
Sahai, E. & Marshall, C. J. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nature Cell Biol.4, 408–415 (2002). CASPubMed Google Scholar
Martin, P. & Parkhurst, S. M. Parallels between tissue repair and embryo morphogenesis. Development131, 3021–3034 (2004). CASPubMed Google Scholar
Qin, Y., Capaldo, C., Gumbiner, B. M. & Macara, I. G. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J. Cell Biol.171, 1061–1071 (2005). CASPubMedPubMed Central Google Scholar
Wells, C. D. et al. A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell125, 535–548 (2006). CASPubMed Google Scholar
Yang, J. & Weinberg, R. A. Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell14, 818–829 (2008). CASPubMed Google Scholar
Ozdamar, B. et al. Regulation of the polarity protein Par6 by TGFβ receptors controls epithelial cell plasticity. Science307, 1603–1609 (2005). Implicates PAR6-dependent proteasomal degradation of RhoA in the onset of TGFβ-induced EMT. CASPubMed Google Scholar
Wang, X. et al. Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-β during the process of epithelial to mesenchymal transition in rat proximal epithelial cells. Biochim. Biophys. Acta1782, 51–59 (2008). CASPubMed Google Scholar
Whiteman, E. L., Liu, C. J., Fearon, E. R. & Margolis, B. The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes. Oncogene27, 3875–3879 (2008). CASPubMedPubMed Central Google Scholar
Wodarz, A. & Nathke, I. Cell polarity in development and cancer. Nature Cell Biol.9, 1016–1024 (2007). CASPubMed Google Scholar
Lee, M. & Vasioukhin, V. Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. J. Cell Sci.121, 1141–1150 (2008). CASPubMed Google Scholar
Hariharan, I. K. & Bilder, D. Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Annu. Rev. Genet.40, 335–361 (2006). CASPubMed Google Scholar
Dow, L. E. & Humbert, P. O. Polarity regulators and the control of epithelial architecture, cell migration, and tumorigenesis. Int. Rev. Cytol.262, 253–302 (2007). CASPubMed Google Scholar
Malliri, A. et al. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature417, 867–871 (2002). CASPubMed Google Scholar
Sahai, E. & Marshall, C. J. RHO–GTPases and cancer. Nature Rev. Cancer2, 133–142 (2002). Google Scholar
Ellenbroek, S. I. & Collard, J. G. Rho GTPases: functions and association with cancer. Clin. Exp. Metastasis24, 657–672 (2007). CASPubMed Google Scholar
Pegtel, D. M. et al. The Par–Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Curr. Biol.17, 1623–1634 (2007). CASPubMed Google Scholar
Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science302, 1704–1709 (2003). CASPubMed Google Scholar
Raftopoulou, M. & Hall, A. Cell migration: Rho GTPases lead the way. Dev. Biol.265, 23–32 (2004). CASPubMed Google Scholar
Trentin, A. G. Thyroid hormone and astrocyte morphogenesis. J. Endocrinol.189, 189–197 (2006). CASPubMed Google Scholar
Etienne-Manneville, S. & Hall, A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCζ. Cell106, 489–498 (2001). References 99–102 identified the sequential signalling of CDC42 and of PAR and Scribble-complex components during wound-induced astrocyte migration. CASPubMed Google Scholar
Etienne-Manneville, S. & Hall, A. Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity. Nature421, 753–756 (2003). CASPubMed Google Scholar
Etienne-Manneville, S., Manneville, J. B., Nicholls, S., Ferenczi, M. A. & Hall, A. Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization. J. Cell Biol.170, 895–901 (2005). CASPubMedPubMed Central Google Scholar
Osmani, N., Vitale, N., Borg, J. P. & Etienne-Manneville, S. Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr. Biol.16, 2395–2405 (2006). CASPubMed Google Scholar
Dow, L. E. et al. The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene26, 2272–2282 (2007). CASPubMed Google Scholar
Shin, K., Wang, Q. & Margolis, B. PATJ regulates directional migration of mammalian epithelial cells. EMBO Rep.8, 158–164 (2007). CASPubMedPubMed Central Google Scholar
Nishimura, T. & Kaibuchi, K. Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Dev. Cell13, 15–28 (2007). CASPubMed Google Scholar
Shen, Y. et al. Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Dev. Cell14, 342–353 (2008). CASPubMed Google Scholar
Nakayama, M. et al. Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation. Dev. Cell14, 205–215 (2008). Shows that Rho–ROCK induces disassembly of the PAR complex and thereby inhibits CDC42-induced RAC1 activation during cell migration. CASPubMed Google Scholar
Jiang, W. et al. p190A RHOGAP is a glycogen synthase kinase-3β substrate required for polarized cell migration. J. Biol. Chem.283, 20978–20988 (2008). CASPubMedPubMed Central Google Scholar
Cau, J. & Hall, A. Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways. J. Cell Sci.118, 2579–2587 (2005). CASPubMed Google Scholar
Pertz, O., Hodgson, L., Klemke, R. L. & Hahn, K. M. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature440, 1069–1072 (2006). CASPubMed Google Scholar
Soloff, R. S., Katayama, C., Lin, M. Y., Feramisco, J. R. & Hedrick, S. M. Targeted deletion of protein kinase C λ reveals a distribution of functions between the two atypical protein kinase C isoforms. J. Immunol.173, 3250–3260 (2004). CASPubMed Google Scholar
Hirose, T. et al. PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. Development133, 1389–1398 (2006). CASPubMed Google Scholar
Sugihara, K. et al. Rac1 is required for the formation of three germ layers during gastrulation. Oncogene17, 3427–3433 (1998). CASPubMed Google Scholar
Chen, F. et al. Cdc42 is required for PIP2-induced actin polymerization and early development but not for cell viability. Curr. Biol.10, 758–765 (2000). CASPubMed Google Scholar
Thumkeo, D. et al. Targeted disruption of the mouse rho-associated kinase 2 gene results in intrauterine growth retardation and fetal death. Mol. Cell. Biol.23, 5043–5055 (2003). CASPubMedPubMed Central Google Scholar
Makarova, O., Roh, M. H., Liu, C. J., Laurinec, S. & Margolis, B. Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1). Gene302, 21–29 (2003). CASPubMed Google Scholar
Roh, M. H. & Margolis, B. Composition and function of PDZ protein complexes during cell polarization. Am. J. Physiol. Renal Physiol.285, F377–F387 (2003). PubMed Google Scholar
Kowalczyk, A. P. & Moses, K. Photoreceptor cells in flies and mammals: Crumby homology? Dev. Cell2, 253–254 (2002). CASPubMed Google Scholar
Tepass, U., Tanentzapf, G., Ward, R. & Fehon, R. Epithelial cell polarity and cell junctions in Drosophila. Annu. Rev. Genet.35, 747–784 (2001). CASPubMed Google Scholar
Fogg, V. C., Liu, C. J. & Margolis, B. Multiple regions of Crumbs3 are required for tight junction formation in MCF10A cells. J. Cell Sci.118, 2859–2869 (2005). CASPubMed Google Scholar
Michel, D. et al. PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells. J. Cell Sci.118, 4049–4057 (2005). CASPubMed Google Scholar
Bilder, D., Li, M. & Perrimon, N. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science289, 113–116 (2000). CASPubMed Google Scholar
Budnik, V. et al. Regulation of synapse structure and function by the Drosophila tumor suppressor gene dlg. Neuron17, 627–640 (1996). CASPubMedPubMed Central Google Scholar
Mathew, D. et al. Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr. Biol.12, 531–539 (2002). CASPubMedPubMed Central Google Scholar
Mertens, A. E., Roovers, R. C. & Collard, J. G. Regulation of Tiam1–Rac signalling. FEBS Lett.546, 11–16 (2003). CASPubMed Google Scholar
Nombela-Arrieta, C. et al. Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing. Immunity21, 429–441 (2004). CASPubMed Google Scholar
Nakaya, Y., Sukowati, E. W., Wu, Y. & Sheng, G. RhoA and microtubule dynamics control cell–basement membrane interaction in EMT during gastrulation. Nature Cell Biol.10, 765–775 (2008). CASPubMed Google Scholar