首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Chemokine triggered integrin activation and actin remodeling events guiding lymphocyte migration across vascular barriers
Authors:Alon Ronen  Shulman Ziv
Institution:aDepartment of Immunology, The Weizmann Institute of Science, Rehovot, 76100 Israel
Abstract:Chemokine signals activate leukocyte integrins and actin remodeling machineries critical for leukocyte adhesion and motility across vascular barriers. The arrest of leukocytes at target blood vessel sites depends on rapid conformational activation of their α4 and β2 integrins by the binding of endothelial-displayed chemokines to leukocyte Gi-protein coupled receptors (GPCRs). A universal regulator of this event is the integrin-actin adaptor, talin1. Chemokine-stimulated GPCRs can transmit within fractions of seconds signals via multiple Rho GTPases, which locally raise plasma membrane levels of the talin activating phosphatidyl inositol, PtdIns(4,5)P2 (PIP2). Additional pools of GPCR stimulated Rac-1 and Rap-1 GTPases together with GPCR stimulated PLC and PI3K family members regulate the turnover of focal contacts of leukocyte integrins, induce the collapse of leukocyte microvilli, and promote polarized leukocyte crawling in search of exit cues. Concomitantly, other leukocyte GTPases trigger invasive protrusions into and between endothelial cells in search of basolateral chemokine exit cues. We will review here major findings and open questions related to these sequential guiding activities of endothelial presented chemokines, focusing mainly on lymphocyte-endothelial interactions as a paradigm for other leukocytes.
Keywords:Abbreviations: Cdc42  cell division cycle 42  GEF  Guanine nucleotide exchange factor  GPCR  G-protein coupled receptor  LFA-1  Leukocyte function-associated antigen-1  LTB4  leukotriene B4  PAF  platelet activating factor  PI3K  Phosphatidylinositol 3-kinase  PIP2  phosphatidylinositol 4  5 bisphosphate  PIP5K  Phosphatidylinositol-4-phosphate 5-kinase  PKC  Protein kinase C  PLC  phopholipase C  RhoA  Ras homology gene family member A  Rac  Ras-related C3 botulinum toxin substrate  Rap-1  Ras-proximate-1  RAPL  regulator of adhesion and cell polarization enriched in lymphoid tissues  RIAM  RAP-1-GTP-interacting adaptor molecule  TEM  transendothelial migration  VLA-4  Very late activation antigen-4
本文献已被 ScienceDirect PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号