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PMID: 14757755 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion.

The Journal of cell biology ·Vol. 164 ·No. 3 ·2004-02-02 ·Pages 461-70

Bivona TG, Wiener HH, Ahearn IM, Silletti J, Chiu VK, Philips MR

Abstract

Rap1 and Ras are closely related GTPases that share some effectors but have distinct functions. We studied the subcellular localization of Rap1 and its sites of activation in living cells. Both GFP-tagged Rap1 and endogenous Rap1 were localized to the plasma membrane (PM) and endosomes. The PM association of GFP-Rap1 was dependent on GTP binding, and GFP-Rap1 was rapidly up-regulated on this compartment in response to mitogens, a process blocked by inhibitors of endosome recycling. A novel fluorescent probe for GTP-bound Rap1 revealed that this GTPase was transiently activated only on the PM of both fibroblasts and T cells. Activation on the PM was blocked by inhibitors of endosome recycling. Moreover, inhibition of endosome recycling blocked the ability of Rap1 to promote integrin-mediated adhesion of T cells. Thus, unlike Ras, the membrane localizations of Rap1 are dynamically regulated, and the PM is the principle platform from which Rap1 signaling emanates. These observations may explain some of the biological differences between these GTPases.

MeSH Terms
Animals Cell Adhesion/physiology Cell Line Cell Membrane/drug effects,metabolism Endosomes/metabolism Enzyme Activation Epidermal Growth Factor/metabolism Exocytosis/physiology Golgi Apparatus/metabolism Guanosine Triphosphate/metabolism Humans Mitogens/pharmacology Protein Structure, Tertiary Recombinant Fusion Proteins/metabolism Subcellular Fractions/chemistry,metabolism T-Lymphocytes/metabolism Up-Regulation rap1 GTP-Binding Proteins/metabolism
Chemicals
Mitogens Recombinant Fusion Proteins Epidermal Growth Factor Guanosine Triphosphate rap1 GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bivona Trever G
Deparment of Cell Biology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA.
Wiener Heidi H
Ahearn Ian M
Silletti Joseph
Chiu Vi K
Philips Mark R
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200311093
Published
2004-02-02
Pages
461-70
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172240
Subset
IM
Grants
NCRR NIH HHS · M01 RR000096 · United States
NIAID NIH HHS · R29 AI036224 · United States
NIGMS NIH HHS · R01 GM055279 · United States
NIGMS NIH HHS · GM55279 · United States
NCRR NIH HHS · M01RR00096 · United States
NIAID NIH HHS · AI36224 · United States
NIAID NIH HHS · R01 AI036224 · United States
External Links
PubMed source DOI: 10.1083/jcb.200311093 PMC Full Text View journal details
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