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PMID: 19373240 Published · ppublish English Research Support, Non-U.S. Gov't Review

Bringing up the rear: defining the roles of the uropod.

Nature reviews. Molecular cell biology ·Vol. 10 ·No. 5 ·2009-00-00 ·Pages 353-9

Sánchez-Madrid F, Serrador JM

Abstract

Renewed interest in cell shape has been prompted by a recent flood of evidence that indicates that cell polarity is essential for the biology of motile cells. The uropod, a protrusion at the rear of amoeboid motile cells such as leukocytes, exemplifies the importance of morphology in cell motility. Remodelling of cell shape by uropod-interfering agents disturbs cell migration. But even though the mechanisms by which uropods regulate cell migration are beginning to emerge, their functional significance remains enigmatic.

MeSH Terms
Animals Cell Movement/genetics,physiology Cell Polarity/genetics,physiology Cell Shape/genetics,physiology Eukaryota/cytology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sánchez-Madrid Francisco
Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. [email protected]
Serrador Juan M
References (82)
82 references, click to expand
  1. Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation.
    J Cell Biol. 2004 Oct 25;167(2):327-37 PMID: 15504914
  2. B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node.
    Immunity. 2007 Jul;27(1):160-71 PMID: 17658276
  3. Spatiotemporal regulation of moesin phosphorylation and rear release by Rho and serine/threonine phosphatase during neutrophil migration.
    Exp Cell Res. 2002 Aug 1;278(1):112-22 PMID: 12126963
  4. Ca2+-dependent myosin II activation is required for uropod retraction during neutrophil migration.
    J Cell Sci. 2000 Apr;113 ( Pt 7):1287-98 PMID: 10704379
  5. Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility.
    Nat Cell Biol. 2009 Jan;11(1):17-26 PMID: 19043408
  6. Perturbation of cell adhesion and microvilli formation by antisense oligonucleotides to ERM family members.
    J Cell Biol. 1994 Jun;125(6):1371-84 PMID: 8207064
  7. Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms.
    J Cell Biol. 2008 Nov 3;183(3):527-42 PMID: 18955551
  8. Chemoattractant-induced changes in surface expression and redistribution of a functional ligand for P-selectin on neutrophils.
    Blood. 1996 Mar 1;87(5):2029-37 PMID: 8634454
  9. Mammalian Rho GTPases: new insights into their functions from in vivo studies.
    Nat Rev Mol Cell Biol. 2008 Sep;9(9):690-701 PMID: 18719708
  10. Phospholipid flip-flop and phospholipid scramblase 1 (PLSCR1) co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils.
    J Biol Chem. 2004 Apr 23;279(17):17625-33 PMID: 14766753
  11. Effect of fever-like whole-body hyperthermia on lymphocyte spectrin distribution, protein kinase C activity, and uropod formation.
    J Immunol. 1999 Mar 15;162(6):3378-87 PMID: 10092792
  12. A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation.
    Immunity. 2005 Jun;22(6):737-48 PMID: 15963788
  13. Lipid rafts mediate biosynthetic transport to the T lymphocyte uropod subdomain and are necessary for uropod integrity and function.
    Blood. 2002 Feb 1;99(3):978-84 PMID: 11807002
  14. Rac1 mediates collapse of microvilli on chemokine-activated T lymphocytes.
    J Immunol. 2004 Oct 15;173(8):4985-93 PMID: 15470041
  15. Microspikes on the lymphocyte uropod.
    Science. 1969 Feb 21;163(3869):818-20 PMID: 5764475
  16. Temporal and spatial regulation of chemotaxis.
    Dev Cell. 2002 Oct;3(4):469-78 PMID: 12408799
  17. Rho GTPase Rac1 is critical for neutrophil migration into the lung.
    Blood. 2007 Feb 1;109(3):1257-64 PMID: 16990606
  18. Role of the cytoskeleton during leukocyte responses.
    Nat Rev Immunol. 2004 Feb;4(2):110-22 PMID: 15040584
  19. Segregation of leading-edge and uropod components into specific lipid rafts during T cell polarization.
    Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9642-7 PMID: 11493690
  20. Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of its deacetylase activity.
    Mol Biol Cell. 2006 Aug;17(8):3435-45 PMID: 16738306
  21. Rapid leukocyte migration by integrin-independent flowing and squeezing.
    Nature. 2008 May 1;453(7191):51-5 PMID: 18451854
  22. ICAM-2 redistributed by ezrin as a target for killer cells.
    Nature. 1996 Jul 18;382(6588):265-8 PMID: 8717043
  23. Leukocyte polarization in cell migration and immune interactions.
    EMBO J. 1999 Feb 1;18(3):501-11 PMID: 9927410
  24. Neutrophil traction stresses are concentrated in the uropod during migration.
    Biophys J. 2007 Apr 1;92(7):L58-60 PMID: 17218464
  25. Identification of a high affinity binding protein for the regulatory subunit RII beta of cAMP-dependent protein kinase in Golgi enriched membranes of human lymphoblasts.
    EMBO J. 1992 May;11(5):1723-31 PMID: 1582408
  26. PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxis.
    Curr Biol. 2008 Jul 22;18(14):1034-43 PMID: 18635356
  27. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils.
    Cell. 2003 Jul 25;114(2):201-14 PMID: 12887922
  28. Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins.
    Blood. 2000 Oct 1;96(7):2528-36 PMID: 11001907
  29. Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway.
    J Cell Biol. 1995 Oct;131(2):495-508 PMID: 7593174
  30. Rho/ROCK and myosin II control the polarized distribution of endocytic clathrin structures at the uropod of moving T lymphocytes.
    J Cell Sci. 2007 Oct 15;120(Pt 20):3534-43 PMID: 17895369
  31. Orchestration of lymphocyte chemotaxis by mitochondrial dynamics.
    J Exp Med. 2006 Dec 25;203(13):2879-86 PMID: 17145957
  32. RhoA is required for monocyte tail retraction during transendothelial migration.
    J Cell Biol. 2001 Jul 9;154(1):147-60 PMID: 11448997
  33. ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands.
    J Cell Biol. 1994 Nov;127(3):867-78 PMID: 7525599
  34. Neutrophil adhesion to E-selectin under shear promotes the redistribution and co-clustering of ADAM17 and its proteolytic substrate L-selectin.
    J Leukoc Biol. 2008 Jan;83(1):99-105 PMID: 17928459
  35. PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils.
    Nat Immunol. 2008 Jul;9(7):743-52 PMID: 18536720
  36. Contraction due to microtubule disruption is associated with increased phosphorylation of myosin regulatory light chain.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10252-6 PMID: 7479762
  37. Direct involvement of ezrin/radixin/moesin (ERM)-binding membrane proteins in the organization of microvilli in collaboration with activated ERM proteins.
    J Cell Biol. 1999 Jun 28;145(7):1497-509 PMID: 10385528
  38. Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils.
    Immunity. 2006 Aug;25(2):285-95 PMID: 16901726
  39. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.
    J Exp Med. 2008 Jan 21;205(1):195-205 PMID: 18195072
  40. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1.
    Nat Cell Biol. 2007 Jan;9(1):36-44 PMID: 17173042
  41. Type I phosphatidylinositol 4-phosphate 5-kinase controls neutrophil polarity and directional movement.
    J Cell Biol. 2007 Dec 31;179(7):1539-53 PMID: 18158329
  42. Microtubule retraction into the uropod and its role in T cell polarization and motility.
    J Immunol. 1997 Aug 1;159(3):1063-7 PMID: 9233597
  43. Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and ICAM-2.
    J Cell Biol. 1998 Feb 23;140(4):885-95 PMID: 9472040
  44. Lymphocyte surface and cytoplasmic changes associated with translational motility and spontaneous capping of Ig.
    J Cell Sci. 1979 Oct;39:137-47 PMID: 316817
  45. Live imaging of chronic inflammation caused by mutation of zebrafish Hai1.
    J Cell Sci. 2007 Oct 1;120(Pt 19):3372-83 PMID: 17881499
  46. A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility.
    Nat Cell Biol. 2002 Jun;4(6):399-407 PMID: 12032545
  47. A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting.
    J Biol Chem. 2002 Mar 22;277(12):10400-9 PMID: 11784723
  48. Multinucleated giant cells generation induced by interferon-gamma. Changes in the expression and distribution of the intercellular adhesion molecule-1 during macrophages fusion and multinucleated giant cell formation.
    Lab Invest. 1994 Nov;71(5):737-44 PMID: 7967525
  49. Septins: cellular and functional barriers of neuronal activity.
    Curr Biol. 2007 Nov 20;17(22):R961-3 PMID: 18029249
  50. Roles of chemokines and receptor polarization in NK-target cell interactions.
    J Immunol. 1998 Oct 1;161(7):3330-9 PMID: 9759849
  51. Chemotaxis: signalling the way forward.
    Nat Rev Mol Cell Biol. 2004 Aug;5(8):626-34 PMID: 15366706
  52. Human immunodeficiency virus type 1 induces cellular polarization, intercellular adhesion molecule-1 redistribution, and multinucleated giant cell generation in human primary monocytes but not in monocyte-derived macrophages.
    Lab Invest. 1996 Dec;75(6):783-90 PMID: 8973473
  53. Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow.
    J Cell Biol. 2003 Apr 28;161(2):417-27 PMID: 12707305
  54. EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins.
    J Biol Chem. 2006 Jul 14;281(28):19665-75 PMID: 16690612
  55. LYMPHOCYTE FOOT APPENDAGE: ITS ROLE IN LYMPHOCYTE FUNCTION AND IN IMMUNOLOGICAL REACTIONS.
    Nature. 1965 Feb 27;205:887-8 PMID: 14293154
  56. Activation of the PKB/AKT pathway by ICAM-2.
    Immunity. 2002 Jan;16(1):51-65 PMID: 11825565
  57. The Golgi apparatus at the cell centre.
    Curr Opin Cell Biol. 2003 Feb;15(1):60-6 PMID: 12517705
  58. Relationship of F-actin distribution to development of polar shape in human polymorphonuclear neutrophils.
    J Cell Biol. 1992 May;117(4):765-74 PMID: 1577856
  59. A single class II myosin modulates T cell motility and stopping, but not synapse formation.
    Nat Immunol. 2004 May;5(5):531-8 PMID: 15064761
  60. Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses.
    J Virol. 2007 Nov;81(22):12582-95 PMID: 17728240
  61. Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts.
    J Virol. 2000 Apr;74(7):3264-72 PMID: 10708443
  62. The role of cathepsin X in the migration and invasiveness of T lymphocytes.
    J Cell Sci. 2008 Aug 15;121(Pt 16):2652-61 PMID: 18664495
  63. Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis.
    Blood. 2006 Oct 15;108(8):2814-20 PMID: 16809619
  64. Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages.
    J Leukoc Biol. 2003 Jun;73(6):830-40 PMID: 12773516
  65. Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization.
    J Cell Biol. 1997 Sep 22;138(6):1409-23 PMID: 9298994
  66. CD2 molecules redistribute to the uropod during T cell scanning: implications for cellular activation and immune surveillance.
    Proc Natl Acad Sci U S A. 2002 May 28;99(11):7582-7 PMID: 12032326
  67. Cyclic guanosine monophosphate-dependent protein kinase is targeted to intermediate filaments and phosphorylates vimentin in A23187-stimulated human neutrophils.
    Blood. 1995 Jan 1;85(1):222-30 PMID: 7803796
  68. Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis.
    Mol Biol Cell. 2007 Dec;18(12):5069-80 PMID: 17928408
  69. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes.
    EMBO J. 1996 Feb 1;15(3):510-9 PMID: 8599934
  70. The PCH family member proline-serine-threonine phosphatase-interacting protein 1 targets to the leukocyte uropod and regulates directed cell migration.
    Mol Biol Cell. 2008 Aug;19(8):3180-91 PMID: 18480402
  71. A role for the neuronal protein collapsin response mediator protein 2 in T lymphocyte polarization and migration.
    J Immunol. 2005 Dec 1;175(11):7650-60 PMID: 16301675
  72. Adenylyl cyclase localization regulates streaming during chemotaxis.
    Cell. 2003 Feb 21;112(4):549-60 PMID: 12600317
  73. CD95 (APO-1/Fas) linkage to the actin cytoskeleton through ezrin in human T lymphocytes: a novel regulatory mechanism of the CD95 apoptotic pathway.
    EMBO J. 2000 Oct 2;19(19):5123-34 PMID: 11013215
  74. The locomotor capacity of human lymphocytes and its enhancement by cell growth.
    Immunology. 1986 Feb;57(2):281-9 PMID: 3081438
  75. Cutting edge: Atypical PKCs regulate T lymphocyte polarity and scanning behavior.
    J Immunol. 2007 Nov 1;179(9):5649-52 PMID: 17947635
  76. Rigidity of circulating lymphocytes is primarily conferred by vimentin intermediate filaments.
    J Immunol. 2001 Jun 1;166(11):6640-6 PMID: 11359818
  77. Cytoskeleton-dependent membrane domain segregation during neutrophil polarization.
    Mol Biol Cell. 2001 Nov;12(11):3550-62 PMID: 11694588
  78. Centriolar location during blood cell spreading and motion in vitro: an ultrastructural analysis.
    J Cell Sci. 1988 Feb;89 ( Pt 2):225-41 PMID: 3263378
  79. PTEN regulates motility but not directionality during leukocyte chemotaxis.
    J Cell Sci. 2004 Dec 1;117(Pt 25):6207-15 PMID: 15564381
  80. ICAMs redistributed by chemokines to cellular uropods as a mechanism for recruitment of T lymphocytes.
    J Cell Biol. 1997 Apr 21;137(2):493-508 PMID: 9128258
  81. Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine.
    J Immunol. 1998 Jul 15;161(2):1026-33 PMID: 9670984
  82. LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment.
    J Cell Sci. 2003 Aug 1;116(Pt 15):3123-33 PMID: 12799414
Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm2680
Email
[email protected]
Published
2009-00-00
Epub
2009-00-17
Pages
353-9
Language
English
Region
England
NLM ID
100962782
Subset
IM
External Links
PubMed source DOI: 10.1038/nrm2680 View journal details
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