Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages
Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk‐like posterior appendage, the uropod. Through time‐lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lame...
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Veröffentlicht in: | Journal of leukocyte biology 2003-06, Vol.73 (6), p.830-840 |
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creator | Ratner, Stuart Piechocki, Marie P. Galy, Anne |
description | Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk‐like posterior appendage, the uropod. Through time‐lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho‐family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant‐negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. The results suggest that one role of Cdc42 in lymphocyte motility is to preserve polarity by concentrating lamellipodial disassembly signals in the uropod. |
doi_str_mv | 10.1189/jlb.1001894 |
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Through time‐lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho‐family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant‐negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. 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Through time‐lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho‐family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant‐negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. The results suggest that one role of Cdc42 in lymphocyte motility is to preserve polarity by concentrating lamellipodial disassembly signals in the uropod.</description><subject>cdc42 GTP-Binding Protein - genetics</subject><subject>cdc42 GTP-Binding Protein - physiology</subject><subject>Cell Movement</subject><subject>Cell Polarity</subject><subject>Cells, Cultured</subject><subject>chemotaxis</subject><subject>cytoskeleton</subject><subject>Genetic Vectors</subject><subject>human</subject><subject>Humans</subject><subject>Kinetics</subject><subject>leukemia</subject><subject>Lymphocyte Activation</subject><subject>motility</subject><subject>Mutation</subject><subject>Pseudopodia - ultrastructure</subject><subject>Retroviridae - genetics</subject><subject>T cell</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - enzymology</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumor Cells, Cultured</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkL1v2zAQxYkiRe0knboXWtIlUHL8sCiNjdF8FAYSBO5MUNTRpkGZqmhDUf_60LCBbu0td8PvvXd4hHyhcENpWd1ufH1DAdIpPpAprXiZ80LyMzIFKWg-EwATch7jBgA4K-ATmVAmJZ_RYkpeXoPHLNjsdR1yq1vnx-xh-aIjZvPGCJa5bdYFr3v3B5sM37oeY3Rhe5D4se3WwYw7zHTX4bbRK4yX5KPVPuLn074gv-5_LOeP-eL54Wn-fZEnUwE5Y9yABWGEYCBpSSVnyKsCDYiqsjNmuawRNKsBZsZCVTfMlDWWvNRgeckvyLejb9eH33uMO9W6aNB7vcWwj0ryNBWD_4K0Yoyl9AReH0HThxh7tKrrXav7UVFQh6ZValqdmk7015Ptvm6x-cueqk0AHIHBeRz_5aV-Lu6g5IdXr46StVutB9ejiq32PiUwNQyD5KpQB-4d27eTUw</recordid><startdate>20030601</startdate><enddate>20030601</enddate><creator>Ratner, Stuart</creator><creator>Piechocki, Marie P.</creator><creator>Galy, Anne</creator><general>Society for Leukocyte Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030601</creationdate><title>Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages</title><author>Ratner, Stuart ; Piechocki, Marie P. ; Galy, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4240-223c0f04c44207181732e396ec0499f52f37be0a2b005cf09bd2c8be838a0f383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>cdc42 GTP-Binding Protein - genetics</topic><topic>cdc42 GTP-Binding Protein - physiology</topic><topic>Cell Movement</topic><topic>Cell Polarity</topic><topic>Cells, Cultured</topic><topic>chemotaxis</topic><topic>cytoskeleton</topic><topic>Genetic Vectors</topic><topic>human</topic><topic>Humans</topic><topic>Kinetics</topic><topic>leukemia</topic><topic>Lymphocyte Activation</topic><topic>motility</topic><topic>Mutation</topic><topic>Pseudopodia - ultrastructure</topic><topic>Retroviridae - genetics</topic><topic>T cell</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - enzymology</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ratner, Stuart</creatorcontrib><creatorcontrib>Piechocki, Marie P.</creatorcontrib><creatorcontrib>Galy, Anne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ratner, Stuart</au><au>Piechocki, Marie P.</au><au>Galy, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>73</volume><issue>6</issue><spage>830</spage><epage>840</epage><pages>830-840</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk‐like posterior appendage, the uropod. Through time‐lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipodia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uropod border. This exclusion of lamellipodia from the uropod required the Rho‐family guanosine triphosphatase Cdc42. Reduction of Cdc42 activity by expression of dominant‐negative Cdc42 resulted in “two headed” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. 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source | Wiley Online Library - AutoHoldings Journals; MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
subjects | cdc42 GTP-Binding Protein - genetics cdc42 GTP-Binding Protein - physiology Cell Movement Cell Polarity Cells, Cultured chemotaxis cytoskeleton Genetic Vectors human Humans Kinetics leukemia Lymphocyte Activation motility Mutation Pseudopodia - ultrastructure Retroviridae - genetics T cell T-Lymphocytes - cytology T-Lymphocytes - enzymology T-Lymphocytes - immunology Tumor Cells, Cultured |
title | Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages |
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