How chemokines invite leukocytes to dance

A prominent activity of the chemokine system is the regulation of leukocyte trafficking. Here we summarize recent findings on the initial steps in chemokine receptor–induced signal transduction in leukocytes. In particular, we discuss the potential influences of the formation of oligomers of ligand and receptor and of coupling between chemokine signals and regulators of the cytoskeleton, such as small GTPases.

[1]  Wei Lu,et al.  Directional Sensing Requires Gβγ-Mediated PAK1 and PIXα-Dependent Activation of Cdc42 , 2003, Cell.

[2]  B. Sykes,et al.  Solution structure and basis for functional activity of stromal cell‐derived factor‐1; dissociation of CXCR4 activation from binding and inhibition of HIV‐1 , 1997, The EMBO journal.

[3]  M. Ratajczak,et al.  SDF-1 responsiveness does not correlate with CXCR4 expression levels of developing human bone marrow B cells. , 1999, Blood.

[4]  C. Sumen,et al.  ReviewIntravital Microscopy : Visualizing Immunity in Context , 2004 .

[5]  H. Bourne,et al.  PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells , 2007, The Journal of cell biology.

[6]  T. Schwartz,et al.  Is there a 'lock' for all agonist 'keys' in 7TM receptors? , 1996, Trends in pharmacological sciences.

[7]  V. Gurevich,et al.  GPCR monomers and oligomers: it takes all kinds , 2008, Trends in Neurosciences.

[8]  Antonio Lanzavecchia,et al.  T cell costimulation by chemokine receptors , 2005, Nature Immunology.

[9]  T. Jin,et al.  Ligand-Induced Partitioning of Human CXCR1 Chemokine Receptors with Lipid Raft Microenvironments Facilitates G-Protein-Dependent Signaling , 2005, Molecular and Cellular Biology.

[10]  Wei Yang,et al.  Hsc/Hsp70 Interacting Protein (Hip) Associates with CXCR2 and Regulates the Receptor Signaling and Trafficking* , 2002, The Journal of Biological Chemistry.

[11]  Caiying Guo,et al.  P-Rex1 Is a Primary Rac2 Guanine Nucleotide Exchange Factor in Mouse Neutrophils , 2005, Current Biology.

[12]  D. Yamazaki,et al.  Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex. , 2006, Journal of biochemistry.

[13]  D. Yamazaki,et al.  PtdIns(3,4,5)P3 binding is necessary for WAVE2-induced formation of lamellipodia , 2004, Nature Cell Biology.

[14]  Tracy M Handel,et al.  Chemokine: receptor structure, interactions, and antagonism. , 2007, Annual review of immunology.

[15]  K. Katagiri,et al.  Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion , 2006, Nature Immunology.

[16]  Dianqing Wu,et al.  Roles of PLC-β2 and -β3 and PI3Kγ in Chemoattractant-Mediated Signal Transduction , 2000 .

[17]  S. Marullo,et al.  Resonance energy transfer approaches in molecular pharmacology and beyond. , 2007, Trends in pharmacological sciences.

[18]  M. Cybulsky,et al.  Getting to the site of inflammation: the leukocyte adhesion cascade updated , 2007, Nature Reviews Immunology.

[19]  Gideon Rechavi,et al.  A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets , 2007, The Journal of experimental medicine.

[20]  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.

[21]  Mark M. Davis,et al.  A single class II myosin modulates T cell motility and stopping, but not synapse formation , 2004, Nature Immunology.

[22]  K. Okkenhaug,et al.  P-Rex1 Regulates Neutrophil Function , 2005, Current Biology.

[23]  A. Valencia,et al.  Filamin-A regulates actin-dependent clustering of HIV receptors , 2007, Nature Cell Biology.

[24]  U. V. von Andrian,et al.  CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo , 2007, The Journal of experimental medicine.

[25]  D. McDermott,et al.  Role for CCR5Δ32 Protein in Resistance to R5, R5X4, and X4 Human Immunodeficiency Virus Type 1 in Primary CD4+ Cells , 2004, Journal of Virology.

[26]  M. Smyth,et al.  A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation. , 2005, Immunity.

[27]  M. Auer,et al.  Transcytosis and Surface Presentation of IL-8 by Venular Endothelial Cells , 1997, Cell.

[28]  M. Groettrup,et al.  Opposite Fate of Endocytosed CCR7 and Its Ligands: Recycling versus Degradation1 , 2006, The Journal of Immunology.

[29]  A. Rot,et al.  Throwing light on DARC. , 2006, Biochemical Society transactions.

[30]  Mark W Dewhirst,et al.  Requirements for T Lymphocyte Migration in Explanted Lymph Nodes1 , 2007, The Journal of Immunology.

[31]  J. Benovic,et al.  The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. , 2003, Developmental cell.

[32]  Ravi S. Misra,et al.  Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes , 2007, The Journal of experimental medicine.

[33]  L. Pirola,et al.  Structure and function of phosphoinositide 3-kinases. , 1998, Biochimica et biophysica acta.

[34]  J. Delon,et al.  Cutting Edge: Atypical PKCs Regulate T Lymphocyte Polarity and Scanning Behavior1 , 2007, The Journal of Immunology.

[35]  M. Baggiolini,et al.  Is Dimerization Of Chemokine Receptors Functionally Relevant? , 2001, Science's STKE.

[36]  Michael D. Cahalan,et al.  Two-photon tissue imaging: seeing the immune system in a fresh light , 2002, Nature Reviews Immunology.

[37]  P. V. van Haastert,et al.  Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum chemotaxis , 2007, The Journal of cell biology.

[38]  M. Parmentier,et al.  Allosteric Transinhibition by Specific Antagonists in , 2007 .

[39]  Silvia Sebastiani,et al.  A rich chemokine environment strongly enhances leukocyte migration and activities. , 2005, Blood.

[40]  B. Ludewig,et al.  CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. , 2004, Blood.

[41]  Phillip T. Hawkins,et al.  Gβγs and the Ras binding domain of p110γ are both important regulators of PI3Kγ signalling in neutrophils , 2006, Nature Cell Biology.

[42]  H. Bourne,et al.  Gαi Is Not Required for Chemotaxis Mediated by Gi-coupled Receptors* , 1999, The Journal of Biological Chemistry.

[43]  Matthew D. Welch,et al.  The ARP2/3 complex: an actin nucleator comes of age , 2006, Nature Reviews Molecular Cell Biology.

[44]  P. Allavena,et al.  Uncoupling of inflammatory chemokine receptors by IL-10: generation of functional decoys , 2000, Nature Immunology.

[45]  Marc Parmentier,et al.  The Core Domain of Chemokines Binds CCR5 Extracellular Domains while Their Amino Terminus Interacts with the Transmembrane Helix Bundle* , 2003, The Journal of Biological Chemistry.

[46]  Timothy N. C. Wells,et al.  Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[47]  M. Uguccioni,et al.  CCL22‐induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first β‐strand of chemokine , 2005, European journal of immunology.

[48]  Alberto Mantovani,et al.  Tuning inflammation and immunity by chemokine sequestration: decoys and more , 2006, Nature Reviews Immunology.

[49]  G. Milligan,et al.  Allosteric modulation of heterodimeric G-protein-coupled receptors. , 2007, Trends in pharmacological sciences.

[50]  B. Sykes,et al.  Neutrophil activation by monomeric interleukin-8. , 1994, Science.

[51]  Kevin Wei,et al.  A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development , 2006, The Journal of experimental medicine.

[52]  Toshikazu Shirai,et al.  Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration , 2001, Nature.

[53]  T. Chun,et al.  Structural and functional characterization of CC chemokine CCL14. , 2007, Biochemistry.

[54]  J. Hartwig,et al.  Filamins as integrators of cell mechanics and signalling , 2001, Nature Reviews Molecular Cell Biology.

[55]  T. Kinashi,et al.  Intracellular signalling controlling integrin activation in lymphocytes , 2005, Nature Reviews Immunology.

[56]  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.

[57]  R. Jessberger,et al.  Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs , 2006, Nature Immunology.

[58]  M. Mandai,et al.  Requirement for Tec Kinases in Chemokine-Induced Migration and Activation of Cdc42 and Rac , 2004, Current Biology.

[59]  K. Kutsche,et al.  αPIX Rho GTPase Guanine Nucleotide Exchange Factor Regulates Lymphocyte Functions and Antigen Receptor Signaling , 2008, Molecular and Cellular Biology.

[60]  M. Thelen,et al.  PI 3-kinase-dependent and independent chemotaxis of human neutrophil leukocytes. , 1995, Biochemical and biophysical research communications.

[61]  A. Mantovani,et al.  Inhibition of Monocyte Chemotaxis to C-C Chemokines by Antisense Oligonucleotide for Cytosolic Phospholipase A(*) , 1996, The Journal of Biological Chemistry.

[62]  Gregory J Babcock,et al.  Ligand-independent Dimerization of CXCR4, a Principal HIV-1 Coreceptor* , 2003, The Journal of Biological Chemistry.

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

[64]  M. Ginsberg,et al.  Integrin activation. , 2008, Biochemical Society transactions.

[65]  M. Bouvier,et al.  Roles of G‐protein‐coupled receptor dimerization , 2004, EMBO reports.

[66]  T. Kenakin,et al.  Inverse, protean, and ligand‐selective agonism: matters of receptor conformation , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[67]  T. Schwartz,et al.  Molecular mechanism of 7TM receptor activation--a global toggle switch model. , 2006, Annual review of pharmacology and toxicology.

[68]  E. Palmesino,et al.  Differences in CXCR4-mediated signaling in B cells. , 2006, Immunobiology.

[69]  國崎 祐哉 DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis , 2006 .

[70]  Michael Sixt,et al.  Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces , 2007, Nature Immunology.

[71]  J. Cyster,et al.  Integrin-dependence of Lymphocyte Entry into the Splenic White Pulp , 2003, The Journal of experimental medicine.

[72]  C. Martínez-A,et al.  A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate–mediated egress , 2007, The Journal of experimental medicine.

[73]  Kuan-Teh Jeang,et al.  Mechanism of Transdominant Inhibition of CCR5-mediated HIV-1 Infection by ccr5Δ32* , 1997, The Journal of Biological Chemistry.

[74]  H. Higgs,et al.  The many faces of actin: matching assembly factors with cellular structures , 2007, Nature Cell Biology.

[75]  P. Proost,et al.  Synergy between proinflammatory ligands of G protein‐coupled receptors in neutrophil activation and migration , 2004, Journal of leukocyte biology.

[76]  R. Xavier,et al.  Wiskott–Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development , 2007, Proceedings of the National Academy of Sciences.

[77]  J. Kehrl Chemoattractant receptor signaling and the control of lymphocyte migration , 2006, Immunologic research.

[78]  B. Nieswandt,et al.  Kindlin-3 is essential for integrin activation and platelet aggregation , 2008, Nature Medicine.

[79]  F. Alt,et al.  WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo , 2005, Journal of leukocyte biology.

[80]  Guttorm Haraldsen,et al.  Coy decoy with a new ploy: Interceptor controls the levels of homeostatic chemokines , 2006, European journal of immunology.

[81]  M. Thelen,et al.  Dancing to the tune of chemokines , 2001, Nature Immunology.

[82]  M. Sixt,et al.  Rapid leukocyte migration by integrin-independent flowing and squeezing , 2008, Nature.

[83]  R. Stevens,et al.  High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor , 2007, Science.

[84]  M. Thelen,et al.  The Chemokine SDF-1/CXCL12 Binds to and Signals through the Orphan Receptor RDC1 in T Lymphocytes* , 2005, Journal of Biological Chemistry.

[85]  John G. Collard,et al.  The Par polarity complex regulates Rap1- and chemokine-induced T cell polarization , 2007, The Journal of cell biology.

[86]  R. Weissleder,et al.  Oligomerization of CXCL10 Is Necessary for Endothelial Cell Presentation and In Vivo Activity1 , 2006, The Journal of Immunology.

[87]  C. Martínez-A,et al.  Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. , 2004, Immunity.

[88]  S. Jameson,et al.  Selective Regulation of CD8 Effector T Cell Migration by the p110γ Isoform of Phosphatidylinositol 3-Kinase1 , 2008, The Journal of Immunology.

[89]  J. Pin,et al.  Asymmetric conformational changes in a GPCR dimer controlled by G‐proteins , 2006, The EMBO journal.

[90]  J. Cyster,et al.  CC Chemokine Receptor 7 Contributes to Gi-Dependent T Cell Motility in the Lymph Node1 , 2007, The Journal of Immunology.

[91]  W L Stanford,et al.  Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. , 2000, Science.

[92]  F. Dumas,et al.  CD4 Interacts Constitutively with Multiple CCR5 at the Plasma Membrane of Living Cells , 2007, Journal of Biological Chemistry.

[93]  P. Loetscher,et al.  Rho kinase is required for CCR7‐mediated polarization and chemotaxis of T lymphocytes , 2003, FEBS Letters.

[94]  R. Staudinger,et al.  Solubilization of the chemokine receptor CXCR4. , 2000, Biochemical and biophysical research communications.

[95]  R. Geha,et al.  WIP and WASP play complementary roles in T cell homing and chemotaxis to SDF-1alpha. , 2006, International immunology.

[96]  M. Baggiolini,et al.  Unusual Chemokine Receptor Antagonism Involving a Mitogen-Activated Protein Kinase Pathway1 , 2004, The Journal of Immunology.

[97]  Matthew F Krummel,et al.  Maintenance and modulation of T cell polarity , 2006, Nature Immunology.

[98]  C. Moratz,et al.  Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. , 2005, Immunity.

[99]  P. Iglesias,et al.  PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. , 2007, Developmental cell.

[100]  Erez Raz,et al.  Control of Chemokine-Guided Cell Migration by Ligand Sequestration , 2008, Cell.

[101]  K. Okkenhaug,et al.  Cutting Edge: Differential Roles for Phosphoinositide 3-Kinases, p110γ and p110δ, in Lymphocyte Chemotaxis and Homing1 , 2004, The Journal of Immunology.

[102]  S. Russell How polarity shapes the destiny of T cells , 2008, Journal of Cell Science.

[103]  Ronald N Germain,et al.  Highways, byways and breadcrumbs: directing lymphocyte traffic in the lymph node. , 2007, Trends in immunology.

[104]  Silvano Sozzani,et al.  Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation , 2000 .

[105]  Jonathan A Javitch,et al.  The Ants Go Marching Two by Two: Oligomeric Structure of G-Protein-Coupled Receptors , 2004, Molecular Pharmacology.

[106]  Peter Friedl,et al.  T Cell Migration in Three-dimensional Extracellular Matrix: Guidance by Polarity and Sensations , 2000, Developmental immunology.

[107]  K. Matsushima,et al.  Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis , 2005, Nature Immunology.

[108]  F. Sánchez‐Madrid,et al.  Control of lymphocyte shape and the chemotactic response by the GTP exchange factor Vav. , 2005, Blood.

[109]  C. Martínez-A,et al.  Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation. , 2001, Annual review of immunology.

[110]  K. Siminovitch,et al.  T Cell Responses in Mammalian Diaphanous-related Formin mDia1 Knock-out Mice* , 2007, Journal of Biological Chemistry.

[111]  M. Oppermann,et al.  G Protein-coupled Receptor Kinases Promote Phosphorylation and β-Arrestin-mediated Internalization of CCR5 Homo- and Hetero-oligomers* , 2005, Journal of Biological Chemistry.

[112]  J. O’Shea,et al.  CXCL12 Signaling Is Independent of Jak2 and Jak3* , 2005, Journal of Biological Chemistry.

[113]  B. Heit,et al.  PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP , 2008, Journal of Cell Science.

[114]  A. Cumano,et al.  Monitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior , 2007, Science.