Phosphoinositide lipids and cell polarity: linking the plasma membrane to the cytocortex.

Many cell types in animals and plants are polarized, which means that the cell is subdivided into functionally and structurally distinct compartments. Epithelial cells, for example, possess an apical side facing a lumen or the outside environment and a basolateral side facing adjacent epithelial cells and the basement membrane. Neurons possess distinct axonal and dendritic compartments with specific functions in sending and receiving signals. Migrating cells form a leading edge that actively engages in pathfinding and cell-substrate attachment, and a trailing edge where such attachments are abandoned. In all of these cases, both the plasma membrane and the cytocortex directly underneath the plasma membrane show differences in their molecular composition and structural organization. In this chapter we will focus on a specific type of membrane lipids, the phosphoinositides, because in polarized cells they show a polarized distribution in the plasma membrane. They furthermore influence the molecular organization of the cytocortex by recruiting specific protein binding partners which are involved in the regulation of the cytoskeleton and in signal transduction cascades that control polarity, growth and cell migration.

[1]  M. Krahn,et al.  Membrane Targeting of Bazooka/PAR-3 Is Mediated by Direct Binding to Phosphoinositide Lipids , 2010, Current Biology.

[2]  A. Burgess,et al.  The PI(3,5)P2 and PI(4,5)P2 interactomes. , 2008, Journal of proteome research.

[3]  Hao Wu,et al.  Par-3-mediated Junctional Localization of the Lipid Phosphatase PTEN Is Required for Cell Polarity Establishment* , 2008, Journal of Biological Chemistry.

[4]  Hao Wu,et al.  PDZ domains of Par-3 as potential phosphoinositide signaling integrators. , 2007, Molecular cell.

[5]  I. Macara,et al.  The PAR proteins: fundamental players in animal cell polarization. , 2007, Developmental cell.

[6]  H. Yin,et al.  Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases , 2007, Pflügers Archiv - European Journal of Physiology.

[7]  J. Engel,et al.  Pseudomonas aeruginosa exploits a PIP3-dependent pathway to transform apical into basolateral membrane , 2007, The Journal of cell biology.

[8]  S. Grinstein,et al.  Alteration of Epithelial Structure and Function Associated with PtdIns(4,5)P2 Degradation by a Bacterial Phosphatase , 2007, The Journal of General Physiology.

[9]  Anirban Datta,et al.  PTEN-Mediated Apical Segregation of Phosphoinositides Controls Epithelial Morphogenesis through Cdc42 , 2007, Cell.

[10]  T. Meyer,et al.  PI(3,4,5)P3 and PI(4,5)P2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane , 2006, Science.

[11]  J. Engel,et al.  Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells , 2006, Nature Cell Biology.

[12]  T. Lecuit,et al.  Spatial control of actin organization at adherens junctions by a synaptotagmin-like protein , 2006, Nature.

[13]  Pascale G. Charest,et al.  Feedback signaling controls leading-edge formation during chemotaxis. , 2006, Current opinion in genetics & development.

[14]  A. Suzuki,et al.  The PAR-aPKC system: lessons in polarity , 2006, Journal of Cell Science.

[15]  L. Collinson,et al.  Regulated and Polarized PtdIns(3,4,5)P3 Accumulation Is Essential for Apical Membrane Morphogenesis in Photoreceptor Epithelial Cells , 2006, Current Biology.

[16]  J. Engel,et al.  The phosphoinositol-3-kinase-protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization. , 2005, Molecular biology of the cell.

[17]  Marion Müller-Borg,et al.  Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling , 2005, Development.

[18]  J. Woodgett Recent advances in the protein kinase B signaling pathway. , 2005, Current opinion in cell biology.

[19]  M. Hoshino,et al.  PAR-6–PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1 , 2005, Nature Cell Biology.

[20]  D. V. van Aalten,et al.  PDK1, the master regulator of AGC kinase signal transduction. , 2004, Seminars in cell & developmental biology.

[21]  Y. Jan,et al.  Hippocampal Neuronal Polarity Specified by Spatially Localized mPar3/mPar6 and PI 3-Kinase Activity , 2003, Cell.

[22]  Marc W. Kirschner,et al.  A PtdInsP3- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity , 2002, Nature Cell Biology.

[23]  Paul Herzmark,et al.  Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils , 2002, Nature Cell Biology.

[24]  Richard A. Firtel,et al.  Spatial and Temporal Regulation of 3-Phosphoinositides by PI 3-Kinase and PTEN Mediates Chemotaxis , 2002, Cell.

[25]  Lewis C Cantley,et al.  The phosphoinositide 3-kinase pathway. , 2002, Science.

[26]  P. Devreotes,et al.  Tumor Suppressor PTEN Mediates Sensing of Chemoattractant Gradients , 2002, Cell.

[27]  G. Panayotou,et al.  Small GTPases and tyrosine kinases coregulate a molecular switch in the phosphoinositide 3-kinase regulatory subunit. , 2002, Cancer cell.

[28]  I. Pass,et al.  Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN. , 2001, Biochemical Society transactions.

[29]  J. Ahringer,et al.  CDC-42 controls early cell polarity and spindle orientation in C. elegans , 2001, Current Biology.

[30]  C. Hunter,et al.  CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans , 2001, Current Biology.

[31]  P. Aspenström,et al.  The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. , 2000, Journal of cell science.

[32]  T. Pawson,et al.  A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity , 2000, Nature Cell Biology.

[33]  G. Joberty,et al.  The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 , 2000, Nature Cell Biology.

[34]  R. Mamillapalli,et al.  Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases , 2000, Current Biology.

[35]  Philip R. Cohen,et al.  Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. , 1998, Science.

[36]  Kenneth M. Yamada,et al.  Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. , 1998, Science.

[37]  M. White,et al.  Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. , 1998, Science.

[38]  C. Der,et al.  Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K , 1997, Nature.

[39]  F. McCormick,et al.  Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. , 1997, Science.

[40]  P. Cohen,et al.  Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα , 1997, Current Biology.

[41]  David R. Kaplan,et al.  Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate , 1997, Science.

[42]  D. Alessi,et al.  Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. , 1996, The Biochemical journal.

[43]  L. Cantley,et al.  Rho Family GTPases Bind to Phosphoinositide Kinases (*) , 1995, The Journal of Biological Chemistry.

[44]  J. Exton,et al.  Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. , 1993, The Journal of biological chemistry.

[45]  P C Sternweis,et al.  Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. , 1991, Science.

[46]  P. Libby,et al.  PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells , 1989, Cell.

[47]  Michael J. Berridge,et al.  Inositol trisphosphate, a novel second messenger in cellular signal transduction , 1984, Nature.

[48]  S. Suetsugu,et al.  Phosphoinositide binding by par-3 involved in par-3 localization. , 2011, Cell structure and function.

[49]  B. Payrastre,et al.  Phosphoinositide signaling pathways: promising role as builders of epithelial cell polarity. , 2009, International review of cell and molecular biology.

[50]  E. Bone,et al.  The role of phosphatidylinositol 4,5 bisphosphate breakdown in cell-surface receptor activation. , 1984, Journal of receptor research.