Cell polarity during motile processes: keeping on track with the exocyst complex.

Motile processes are critical for several physiological and pathological situations such as embryonic development, tumour dissemination and metastasis. Migrating cells, or developing neurons, need to establish front-rear polarity consisting of actin-driven extension of the leading edge and traffic of components that are essential for membrane extension and cell adhesion at the front. Previously, several studies have suggested that the exocyst complex is critical for the establishment and maintenance of cell polarity. This octameric complex controls the docking and insertion of exocytic vesicles to growing areas of the plasma membrane. The aim of the present review is to detail recent advances concerning the molecular and structural organization of the exocyst complex that help to elucidate its role in cell polarity. We will also review the function of the exocyst complex and some of its key interacting partners [including the small GTP-binding protein Ral, aPKCs (atypical protein kinase Cs) and proteins involved in actin assembly] in the formation of plasma extensions at the leading edge, growth cone formation during axonal extension and generation of cell movement.

[1]  C. Rossé,et al.  Manipulating signal delivery – plasma-membrane ERK activation in aPKC-dependent migration , 2010, Journal of Cell Science.

[2]  S. Gupton,et al.  Integrin signaling switches the cytoskeletal and exocytic machinery that drives neuritogenesis. , 2010, Developmental cell.

[3]  R. Dominguez,et al.  Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3* , 2010, The Journal of Biological Chemistry.

[4]  C. Rossé,et al.  PKC and the control of localized signal dynamics , 2010, Nature Reviews Molecular Cell Biology.

[5]  A. Nakano,et al.  Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3 , 2010, Nature Structural &Molecular Biology.

[6]  D. Scott,et al.  RalA-Exocyst Complex Regulates Integrin-Dependent Membrane Raft Exocytosis and Growth Signaling , 2010, Current Biology.

[7]  S. Kimura,et al.  M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex , 2009, Nature Cell Biology.

[8]  Peter J. Parker,et al.  An aPKC-Exocyst Complex Controls Paxillin Phosphorylation and Migration through Localised JNK1 Activation , 2009, PLoS biology.

[9]  Phillip R. Gordon-Weeks,et al.  Cytoskeletal dynamics in growth-cone steering , 2009, Journal of Cell Science.

[10]  Philippe Chavrier,et al.  Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia , 2009, Journal of Cell Science.

[11]  Wei Guo,et al.  The role of the exocyst in matrix metalloproteinase secretion and actin dynamics during tumor cell invadopodia formation. , 2009, Molecular biology of the cell.

[12]  G. Lalli RalA and the exocyst complex influence neuronal polarity through PAR-3 and aPKC , 2009, Journal of Cell Science.

[13]  D. Devos,et al.  Conservation of Helical Bundle Structure between the Exocyst Subunits , 2009, PloS one.

[14]  P. Jeffrey,et al.  Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex , 2009, Nature Structural &Molecular Biology.

[15]  E. Hodneland,et al.  Tunneling nanotube (TNT)-like structures facilitate a constitutive, actomyosin-dependent exchange of endocytic organelles between normal rat kidney cells. , 2008, Experimental cell research.

[16]  M. White,et al.  Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs , 2008, The EMBO journal.

[17]  P. Brennwald,et al.  The ghost in the machine: small GTPases as spatial regulators of exocytosis. , 2008, Trends in cell biology.

[18]  C. Yeaman,et al.  Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration , 2008, Journal of Cell Science.

[19]  Jean-Baptiste Sibarita,et al.  The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA , 2008, The Journal of cell biology.

[20]  M. Carlier,et al.  Regulation of actin assembly associated with protrusion and adhesion in cell migration. , 2008, Physiological reviews.

[21]  David B Sacks,et al.  IQGAP1 Stimulates Proliferation and Enhances Tumorigenesis of Human Breast Epithelial Cells* , 2008, Journal of Biological Chemistry.

[22]  J. Hancock,et al.  Reassessing the Role of Phosphocaveolin‐1 in Cell Adhesion and Migration , 2007, Traffic.

[23]  Susumu Mori,et al.  Filopodia are required for cortical neurite initiation , 2007, Nature Cell Biology.

[24]  D. Scott,et al.  Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts , 2007, Nature Cell Biology.

[25]  Wei Guo,et al.  Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells. , 2007, Molecular biology of the cell.

[26]  Wei Guo,et al.  Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane , 2007, The EMBO journal.

[27]  Marta C Guadamillas,et al.  Integrin regulation of caveolin function , 2007, Journal of cellular and molecular medicine.

[28]  Frank B Gertler,et al.  Filopodia: The Fingers That Do the Walking , 2007, Science's STKE.

[29]  Zhaohui Xu,et al.  The crystal structure of mouse Exo70 reveals unique features of the mammalian exocyst. , 2007, Journal of molecular biology.

[30]  J. Rizo,et al.  Structural Analysis of Conserved Oligomeric Golgi Complex Subunit 2* , 2007, Journal of Biological Chemistry.

[31]  H. Gerdes,et al.  Tunneling nanotubes: A new route for the exchange of components between animal cells , 2007, FEBS letters.

[32]  C. Waterman-Storer,et al.  Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases , 2007, The Journal of cell biology.

[33]  H. Cai,et al.  Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. , 2007, Developmental cell.

[34]  M. Schwartz,et al.  Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. , 2007, Trends in cell biology.

[35]  Kenneth M. Yamada,et al.  Polymerizing Actin Fibers Position Integrins Primed to Probe for Adhesion Sites , 2007, Science.

[36]  Wei Guo,et al.  Exo70 interacts with the Arp2/3 complex and regulates cell migration , 2006, Nature Cell Biology.

[37]  Pietro De Camilli,et al.  Phosphoinositides in cell regulation and membrane dynamics , 2006, Nature.

[38]  M. White,et al.  RalB GTPase-Mediated Activation of the IκB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival , 2006, Cell.

[39]  Peter Novick,et al.  The exocyst defrocked, a framework of rods revealed , 2006, Nature Structural &Molecular Biology.

[40]  D. Brewer,et al.  The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles , 2006, Nature Structural &Molecular Biology.

[41]  D. Sacks,et al.  IQGAP1 in cellular signaling: bridging the GAP. , 2006, Trends in cell biology.

[42]  J. Hancock,et al.  Biogenesis of caveolae: a structural model for caveolin-induced domain formation , 2006, Journal of Cell Science.

[43]  K. Rottner,et al.  The making of filopodia. , 2006, Current opinion in cell biology.

[44]  M. White,et al.  RalB Mobilizes the Exocyst To Drive Cell Migration , 2006, Molecular and Cellular Biology.

[45]  A. Hall,et al.  Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex , 2005, The Journal of cell biology.

[46]  D. Murray,et al.  Plasma membrane phosphoinositide organization by protein electrostatics , 2005, Nature.

[47]  A. West,et al.  Crystal structure of the S.cerevisiae exocyst component Exo70p. , 2005, Journal of molecular biology.

[48]  Sunil Q. Mehta,et al.  Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo , 2005, Nature Structural &Molecular Biology.

[49]  Mala Murthy,et al.  Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. , 2005, Developmental cell.

[50]  Richard G. W. Anderson,et al.  Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization , 2005, Nature Cell Biology.

[51]  Axel T Brunger,et al.  Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase , 2005, The EMBO journal.

[52]  M. Shipitsin,et al.  Activation of RalA is critical for Ras-induced tumorigenesis of human cells. , 2005, Cancer cell.

[53]  R. Chanet,et al.  Protein interaction mapping: a Drosophila case study. , 2005, Genome research.

[54]  P. Novick,et al.  Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p , 2004, The Journal of cell biology.

[55]  J. Bonifacino,et al.  The Mechanisms of Vesicle Budding and Fusion , 2004, Cell.

[56]  P. Chavrier,et al.  ARF6 controls post-endocytic recycling through its downstream exocyst complex effector , 2003, The Journal of cell biology.

[57]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[58]  David G. Drubin,et al.  A Pathway for Association of Receptors, Adaptors, and Actin during Endocytic Internalization , 2003, Cell.

[59]  A. Ridley,et al.  IQGAP1 Promotes Cell Motility and Invasion* , 2003, Journal of Biological Chemistry.

[60]  M. Parat,et al.  Differential caveolin-1 polarization in endothelial cells during migration in two and three dimensions. , 2003, Molecular biology of the cell.

[61]  R. Scheller,et al.  Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex , 2003, The EMBO journal.

[62]  Alan R. Saltiel,et al.  The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin , 2003, Nature.

[63]  A. Hall,et al.  Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity , 2003, Nature.

[64]  Mala Murthy,et al.  Mutations in the Exocyst Component Sec5 Disrupt Neuronal Membrane Traffic, but Neurotransmitter Release Persists , 2003, Neuron.

[65]  A. Hall,et al.  Cell polarity: Par6, aPKC and cytoskeletal crosstalk. , 2003, Current opinion in cell biology.

[66]  W. Guo,et al.  Conservation and Specialization The Role of the Exocyst in Neuronal Exocytosis , 2003, Neuron.

[67]  Klemens Rottner,et al.  The lamellipodium: where motility begins. , 2002, Trends in cell biology.

[68]  Kazuki Nabeshima,et al.  Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts. , 2002, Cancer letters.

[69]  C. Yeaman,et al.  Sec6/8 complexes on trans-Golgi network and plasma membrane regulate late stages of exocytosis in mammalian cells , 2001, The Journal of cell biology.

[70]  W. Kabsch,et al.  The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast. , 2001, Structure.

[71]  Roger L. Williams,et al.  Crystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ , 2000, Cell.

[72]  P. Friedl,et al.  The biology of cell locomotion within three-dimensional extracellular matrix , 2000, Cellular and Molecular Life Sciences CMLS.

[73]  Joan E. Adamo,et al.  The Rho GTPase Rho3 has a direct role in exocytosis that is distinct from its role in actin polarity. , 1999, Molecular biology of the cell.

[74]  R. Scheller,et al.  The sec6/8 Complex Is Located at Neurite Outgrowth and Axonal Synapse-Assembly Domains , 1999, The Journal of Neuroscience.

[75]  P. Novick,et al.  The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis , 1999, The EMBO journal.

[76]  R. Scheller,et al.  Subunit Composition, Protein Interactions, and Structures of the Mammalian Brain sec6/8 Complex and Septin Filaments , 1998, Neuron.

[77]  R. Scheller,et al.  Subunit structure of the mammalian exocyst complex. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[78]  P. Novick,et al.  The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae. , 1996, The EMBO journal.

[79]  M. Bretscher Moving Membrane up to the Front of Migrating Cells , 1996, Cell.

[80]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[81]  A. Wittinghofer,et al.  The 2.2 Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with RaplA and a GTP analogue , 1995, Nature.

[82]  G. Banker,et al.  The establishment of polarity by hippocampal neurons in culture , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[83]  P. Lappalainen,et al.  Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. , 2010, Physiological reviews.

[84]  P. Robinson,et al.  Ral: mediator of membrane trafficking. , 2006, The international journal of biochemistry & cell biology.

[85]  P. Novick,et al.  The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif , 2005, Nature Structural &Molecular Biology.

[86]  C. Rossé,et al.  The exocyst is a Ral effector complex , 2002, Nature Cell Biology.

[87]  A. Iwamatsu,et al.  The exocyst complex binds the small GTPase RalA to mediate filopodia formation , 2002, Nature Cell Biology.