Role of the cytoskeleton during leukocyte responses

The cytoskeleton is a cellular network of structural, adaptor and signalling molecules that regulates most cellular functions that are related to the immune response, including migration, extravasation, antigen recognition, activation and phagocytosis by different subsets of leukocytes. Recently, a large number of regulatory elements and structural constituents of the leukocyte cytoskeleton have been identified. In this review, we discuss the composition and regulation of the different cytoskeletal elements and their role in immune responses.

[1]  K. Beningo,et al.  A contractile activity that closes phagosomes in macrophages. , 1999, Journal of cell science.

[2]  G. Kansas,et al.  The cytoplasmic domain of L-selectin interacts with cytoskeletal proteins via alpha-actinin: receptor positioning in microvilli does not require interaction with alpha-actinin , 1995, The Journal of cell biology.

[3]  María Yáñez-Mó,et al.  ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1. , 2002, Immunity.

[4]  R. Cummings,et al.  Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[5]  C. Figdor,et al.  Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1. , 1997, Molecular biology of the cell.

[6]  T. Tsuruo,et al.  Actin cleavage by CPP-32/apopain during the development of apoptosis , 1997, Oncogene.

[7]  Fumio Matsumura,et al.  Phosphorylation of Myosin-Binding Subunit (Mbs) of Myosin Phosphatase by Rho-Kinase in Vivo , 1999, The Journal of cell biology.

[8]  Z. Brown,et al.  Chemokine Receptors , 2006, Treatments in respiratory medicine.

[9]  S. Chien,et al.  Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression , 2002, The EMBO journal.

[10]  L. Tsai,et al.  Serine 732 Phosphorylation of FAK by Cdk5 Is Important for Microtubule Organization, Nuclear Movement, and Neuronal Migration , 2003, Cell.

[11]  D. McDonald,et al.  Recruitment of HIV and Its Receptors to Dendritic Cell-T Cell Junctions , 2003, Science.

[12]  María Yáñez-Mó,et al.  Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes , 2002, The Journal of cell biology.

[13]  Gary G. Borisy,et al.  Mechanism of filopodia initiation by reorganization of a dendritic network , 2003, The Journal of cell biology.

[14]  R. Flavell,et al.  Deficiency of Small Gtpase Rac2 Affects T Cell Activation , 2001, The Journal of experimental medicine.

[15]  M. Wick,et al.  Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Schmid-Schönbein,et al.  The leukocyte response to fluid stress. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Griffiths,et al.  Lytic granules, secretory lysosomes and disease. , 2003, Current opinion in immunology.

[18]  Daniel Zicha,et al.  A Role for Cdc42 in Macrophage Chemotaxis , 1998, The Journal of cell biology.

[19]  A. Hall,et al.  Rho GTPases in cell biology , 2002, Nature.

[20]  T. Tsuruo,et al.  Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow , 2003, The Journal of cell biology.

[21]  Y. Volkov,et al.  Crucial importance of PKC-β(I) in LFA-1–mediated locomotion of activated T cells , 2001, Nature Immunology.

[22]  N. Hogg,et al.  Vav1 transduces TCR signals required for LFA‐1 function and cell polarization at the immunological synapse , 2003, European journal of immunology.

[23]  E. Caron,et al.  Rho-Kinase and Myosin-II Control Phagocytic Cup Formation during CR, but Not FcγR, Phagocytosis , 2002, Current Biology.

[24]  K. Schwarz,et al.  The interaction between Cdc42 and WASP is required for SDF-1-induced T-lymphocyte chemotaxis. , 2001, Blood.

[25]  S. Bagrodia,et al.  The Dbl-related Protein, Lfc, Localizes to Microtubules and Mediates the Activation of Rac Signaling Pathways in Cells* , 1999, The Journal of Biological Chemistry.

[26]  Giulio Superti-Furga,et al.  Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling , 1999, Nature.

[27]  A. DeFranco,et al.  Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn , 2000, The Journal of experimental medicine.

[28]  R. Germain,et al.  Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin. , 2001, Immunity.

[29]  D. Mccormick Sequence the Human Genome , 1986, Bio/Technology.

[30]  D. C. Edwards,et al.  Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics , 1999, Nature Cell Biology.

[31]  C. Martínez-A,et al.  Cell death during lymphocyte development and activation. , 2003, Seminars in immunology.

[32]  K. Siminovitch,et al.  The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse. , 2003, Immunity.

[33]  J. Wehland,et al.  Fyn-Binding Protein (Fyb)/Slp-76–Associated Protein (Slap), Ena/Vasodilator-Stimulated Phosphoprotein (Vasp) Proteins and the Arp2/3 Complex Link T Cell Receptor (Tcr) Signaling to the Actin Cytoskeleton , 2000, The Journal of cell biology.

[34]  N. Hogg,et al.  LFA-1–mediated Adhesion Is Regulated by Cytoskeletal Restraint and by a Ca2+-dependent Protease, Calpain , 1998, The Journal of cell biology.

[35]  Eric J Kunkel,et al.  Chemokines and the tissue-specific migration of lymphocytes. , 2002, Immunity.

[36]  K. Schuebel,et al.  S. typhimurium Encodes an Activator of Rho GTPases that Induces Membrane Ruffling and Nuclear Responses in Host Cells , 1998, Cell.

[37]  B. Oakley,et al.  Microtubule nucleation. , 2003, Current opinion in cell biology.

[38]  R. Cerione,et al.  Cdc42 Is a Substrate for Caspases and Influences Fas-induced Apoptosis* , 2001, The Journal of Biological Chemistry.

[39]  J. Olivo-Marin,et al.  The membrane-microfilament linker ezrin is involved in the formation of the immunological synapse and in T cell activation. , 2001, Immunity.

[40]  P. Cossart,et al.  Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation , 1999, Current Biology.

[41]  V. Fadok,et al.  The phagocytosis of apoptotic cells. , 2001, Seminars in immunology.

[42]  S. Gordon,et al.  Recognizing death: the phagocytosis of apoptotic cells. , 1998, Trends in cell biology.

[43]  A. Ridley,et al.  Requirement for Rho GTPases and PI 3-kinases during apoptotic cell phagocytosis by macrophages , 2001, Current Biology.

[44]  M. Miyazaki,et al.  Cutting Edge: Negative Regulation of Immune Synapse Formation by Anchoring Lipid Raft to Cytoskeleton Through Cbp-EBP50-ERM Assembly1 , 2002, The Journal of Immunology.

[45]  P. Krammer,et al.  Function and regulation of the CD95 (APO-1/Fas) ligand in the immune system. , 2003, Seminars in immunology.

[46]  T. Hamblin,et al.  Adaptor protein 3–dependent microtubule-mediated movement of lytic granules to the immunological synapse , 2003, Nature Immunology.

[47]  H. Higgs,et al.  The Mouse Formin mDia1 Is a Potent Actin Nucleation Factor Regulated by Autoinhibition , 2003, Current Biology.

[48]  Y. Zheng,et al.  Cloning and Characterization of GEF-H1, a Microtubule-associated Guanine Nucleotide Exchange Factor for Rac and Rho GTPases* , 1998, The Journal of Biological Chemistry.

[49]  M. Hung,et al.  Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells , 2001, Nature Cell Biology.

[50]  G. Bokoch,et al.  Inhibition of myosin light chain kinase by p21-activated kinase. , 1999, Science.

[51]  Keith Burridge,et al.  RhoA is required for monocyte tail retraction during transendothelial migration , 2001, The Journal of cell biology.

[52]  J. Chant,et al.  Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[53]  M. Hengartner,et al.  Candidate Adaptor Protein CED-6 Promotes the Engulfment of Apoptotic Cells in C. elegans , 1998, Cell.

[54]  T. Matsui,et al.  Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases , 1999, Current Biology.

[55]  John G. Collard,et al.  Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading , 1999, Nature Cell Biology.

[56]  S. Grinstein,et al.  Elimination of host cell PtdIns(4,5)P2 by bacterial SigD promotes membrane fission during invasion by Salmonella , 2002, Nature Cell Biology.

[57]  J. Slot,et al.  Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes , 1991, The Journal of experimental medicine.

[58]  Adrian J. Thrasher,et al.  Wasp in immune-system organization and function , 2002, Nature Reviews Immunology.

[59]  J W Sedat,et al.  Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis. , 1999, Molecular biology of the cell.

[60]  P. Caroni,et al.  Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase , 1998, Nature.

[61]  E. Reinherz,et al.  T‐cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection , 1997, The EMBO journal.

[62]  Rangarajan Sampath,et al.  Cytoskeletal Interactions with the Leukocyte Integrin β2 Cytoplasmic Tail , 1998, The Journal of Biological Chemistry.

[63]  T. Mitchison,et al.  Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation. , 1998, Science.

[64]  K. Yamada,et al.  Cutting Edge: Integration of Human T Lymphocyte Cytoskeleton by the Cytolinker Plectin , 2001, The Journal of Immunology.

[65]  Colin R. F. Monks,et al.  Three-dimensional segregation of supramolecular activation clusters in T cells , 1998, Nature.

[66]  M. Coleman,et al.  Rho GTPase signalling pathways in the morphological changes associated with apoptosis , 2002, Cell Death and Differentiation.

[67]  J. Berg,et al.  A millennial myosin census. , 2001, Molecular biology of the cell.

[68]  T. Pollard,et al.  Cellular Motility Driven by Assembly and Disassembly of Actin Filaments , 2003, Cell.

[69]  R. Alon,et al.  Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines , 2001, Nature Immunology.

[70]  K. Katagiri,et al.  RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1 , 2003, Nature Immunology.

[71]  S. Takahashi,et al.  ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. , 2001, Immunity.

[72]  E. Haddad,et al.  Defective Granule Exocytosis in Rab27a-Deficient Lymphocytes from Ashen Mice , 2001, The Journal of cell biology.

[73]  M. Martínez-Lorenzo,et al.  Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella , 2001, Cellular microbiology.

[74]  E. Fuchs,et al.  A structural scaffolding of intermediate filaments in health and disease. , 1998, Science.

[75]  Laura M. Machesky,et al.  Scar1 and the related Wiskott–Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex , 1998, Current Biology.

[76]  Steffen Jung,et al.  Spatial Organization of Signal Transduction Molecules in the NK Cell Immune Synapses During MHC Class I-Regulated Noncytolytic and Cytolytic Interactions , 2001, The Journal of Immunology.

[77]  K. Kaibuchi,et al.  Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association , 1998, The Journal of cell biology.

[78]  F. Sánchez‐Madrid,et al.  A Role for the Rho-p160 Rho Coiled-Coil Kinase Axis in the Chemokine Stromal Cell-Derived Factor-1α-Induced Lymphocyte Actomyosin and Microtubular Organization and Chemotaxis1 , 2002, The Journal of Immunology.

[79]  Zheng Zhou,et al.  CED-1 Is a Transmembrane Receptor that Mediates Cell Corpse Engulfment in C. elegans , 2001, Cell.

[80]  D. Williams,et al.  Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. , 1999, Immunity.

[81]  E. Sahai,et al.  Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I , 2001, Nature Cell Biology.

[82]  L. Machesky,et al.  Rab27a Is Required for Regulated Secretion in Cytotoxic T Lymphocytes , 2001, The Journal of cell biology.

[83]  C. Voermans,et al.  Leukocyte-Endothelium Interaction Promotes SDF-1-dependent Polarization of CXCR4* , 2003, Journal of Biological Chemistry.

[84]  D. Kioussis,et al.  The GTPase Rac-1 controls cell fate in the thymus by diverting thymocytes from positive to negative selection. , 2001, Immunity.

[85]  P. Berche,et al.  Fate of Listeria monocytogenes in murine macrophages: evidence for simultaneous killing and survival of intracellular bacteria , 1994, Infection and immunity.

[86]  C. Cabañas,et al.  ICAMs Redistributed by Chemokines to Cellular Uropods as a Mechanism for Recruitment of T Lymphocytes , 1997, The Journal of cell biology.

[87]  F. Sánchez‐Madrid,et al.  Polarization of Chemokine Receptors to the Leading Edge during Lymphocyte Chemotaxis , 1997, The Journal of experimental medicine.

[88]  J. Galán,et al.  A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion , 1999, Nature.

[89]  J. Bertoglio,et al.  Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing , 2001, Nature Cell Biology.

[90]  P. Janmey,et al.  Actin-binding protein requirement for cortical stability and efficient locomotion. , 1992, Science.

[91]  C Kinnon,et al.  Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis. , 2000, Blood.

[92]  François Nédélec,et al.  Self-organisation and forces in the microtubule cytoskeleton. , 2003, Current opinion in cell biology.

[93]  F. Sánchez‐Madrid,et al.  Leukocyte polarization in cell migration and immune interactions , 1999, The EMBO journal.

[94]  Mitsuhiro Osame,et al.  Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton , 2003, Science.

[95]  Miguel Vicente-Manzanares,et al.  Cutting Edge: Association of the Motor Protein Nonmuscle Myosin Heavy Chain-IIA with the C Terminus of the Chemokine Receptor CXCR4 in T Lymphocytes1 , 2002, The Journal of Immunology.

[96]  A. Hall,et al.  The GTPase Rho has a critical regulatory role in thymus development , 1997, The EMBO journal.

[97]  Yoshiharu Matsuura,et al.  Phosphorylation and Activation of Myosin by Rho-associated Kinase (Rho-kinase)* , 1996, The Journal of Biological Chemistry.

[98]  Matthew L. Albert,et al.  αvβ5 integrin recruits the CrkII–Dock180–Rac1 complex for phagocytosis of apoptotic cells , 2000, Nature Cell Biology.

[99]  M. Poenie,et al.  Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. , 2002, Immunity.

[100]  M. Coughlin,et al.  The contribution of adhesion forces to the leukocyte response to shear stress , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[101]  R. Hayward,et al.  Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella , 1999, The EMBO journal.

[102]  R. Fässler,et al.  The integrin–actin connection, an eternal love affair , 2003, The EMBO journal.

[103]  K. Nakao,et al.  p140mDia, a mammalian homolog of Drosophila diaphanous,is a target protein for Rho small GTPase and is a ligand for profilin , 1997, The EMBO journal.

[104]  A. Weiss,et al.  Cytoskeletal Polarization of T Cells Is Regulated by an Immunoreceptor Tyrosine-based Activation Motif–dependent Mechanism , 1998, The Journal of cell biology.

[105]  Alissa M. Weaver,et al.  Integration of signals to the Arp2/3 complex. , 2003, Current opinion in cell biology.

[106]  Dianqing Wu,et al.  Neutrophils lacking phosphoinositide 3-kinase γ show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[107]  O. Barreiro,et al.  A Novel Serine-rich Motif in the Intercellular Adhesion Molecule 3 Is Critical for Its Ezrin/Radixin/Moesin-directed Subcellular Targeting* , 2002, The Journal of Biological Chemistry.

[108]  J. Galán,et al.  Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. , 1999, Science.

[109]  O. Barreiro,et al.  The RhoA Effector mDia Is Induced During T Cell Activation and Regulates Actin Polymerization and Cell Migration in T Lymphocytes 1 , 2003, The Journal of Immunology.

[110]  H. Horvitz,et al.  CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans , 2000, Nature Cell Biology.

[111]  P. Cossart,et al.  Actin-based motility of vaccinia virus , 1995, Nature.

[112]  D. McDonald,et al.  Visualization of the intracellular behavior of HIV in living cells , 2002, The Journal of cell biology.

[113]  Patricia L. Widder,et al.  A Novel Adaptor Protein Orchestrates Receptor Patterning and Cytoskeletal Polarity in T-Cell Contacts , 1998, Cell.

[114]  Shiro Suetsugu,et al.  WAVE, a novel WASP‐family protein involved in actin reorganization induced by Rac , 1998, The EMBO journal.

[115]  M. Titus,et al.  A role for myosin VII in dynamic cell adhesion , 2001, Current Biology.

[116]  M. Ahmadian,et al.  Characterization of p190RhoGEF, A RhoA-specific Guanine Nucleotide Exchange Factor That Interacts with Microtubules* , 2001, The Journal of Biological Chemistry.

[117]  P. Matarrese,et al.  CD95 (APO‐1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway , 2000, The EMBO journal.

[118]  J. Hartwig,et al.  WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation. , 2002, Immunity.

[119]  A. Ridley,et al.  The Cytoplasmic Tail of L-selectin Interacts with Members of the Ezrin-Radixin-Moesin (ERM) Family of Proteins , 2002, The Journal of Biological Chemistry.

[120]  D. Olive,et al.  Role of ICAM-3 in the initial interaction of T lymphocytes and APCs , 2002, Nature Immunology.

[121]  N. Hirokawa,et al.  A Novel Motor, KIF13A, Transports Mannose-6-Phosphate Receptor to Plasma Membrane through Direct Interaction with AP-1 Complex , 2000, Cell.

[122]  M. Yáñez-Mó,et al.  Involvement of phosphatidylinositol 3-kinase in stromal cell-derived factor-1 alpha-induced lymphocyte polarization and chemotaxis. , 1999, Journal of immunology.

[123]  G M Bokoch,et al.  Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. , 1997, Science.

[124]  S. Narumiya,et al.  Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. , 1999, Science.

[125]  Kyong-Tai Kim,et al.  G protein-coupled receptor signalling and cross-talk: achieving rapidity and specificity. , 2002, Cellular signalling.

[126]  R. Cummings,et al.  Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. , 1997, The Journal of clinical investigation.

[127]  A. DeFranco,et al.  A Critical Role for Syk in Signal Transduction and Phagocytosis Mediated by Fcγ Receptors on Macrophages , 1997, The Journal of experimental medicine.

[128]  M J Brown,et al.  Rigidity of Circulating Lymphocytes Is Primarily Conferred by Vimentin Intermediate Filaments , 2001, The Journal of Immunology.

[129]  B. Moss,et al.  High-speed mass transit for poxviruses on microtubules , 2001, Nature Cell Biology.

[130]  Balbino Alarcón,et al.  Recruitment of Nck by CD3ϵ Reveals a Ligand-Induced Conformational Change Essential for T Cell Receptor Signaling and Synapse Formation , 2002, Cell.

[131]  F. Matsumura,et al.  Specific Localization of Serine 19 Phosphorylated Myosin II during Cell Locomotion and Mitosis of Cultured Cells , 1998, The Journal of cell biology.

[132]  John G. Collard,et al.  Rac Downregulates Rho Activity: Reciprocal Balance between Both Gtpases Determines Cellular Morphology and Migratory Behavior , 1999 .

[133]  B. Finlay,et al.  Microbial pathogenesis and cytoskeletal function , 2003, Nature.

[134]  Asma Nusrat,et al.  Leukocyte transendothelial migration: a junctional affair. , 2002, Seminars in immunology.

[135]  R. McEver Selectins: lectins that initiate cell adhesion under flow. , 2002, Current opinion in cell biology.

[136]  G. Griffiths,et al.  The immunological synapse of CTL contains a secretory domain and membrane bridges. , 2001, Immunity.

[137]  T. Mitchison,et al.  Microtubule polymerization dynamics. , 1997, Annual review of cell and developmental biology.