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PMID: 12356873 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology.

The Journal of cell biology ·Vol. 158 ·No. 7 ·2002-09-30 ·Pages 1299-309

Kazarov AR, Yang X, Stipp CS, Sehgal B, Hemler ME

Abstract

The alpha 3 beta 1 integrin shows strong, stoichiometric, direct lateral association with the tetraspanin CD151. As shown here, an extracellular CD151 site (QRD(194-196)) is required for strong (i.e., Triton X-100-resistant) alpha 3 beta 1 association and for maintenance of a key CD151 epitope (defined by monoclonal antibody TS151r) that is blocked upon alpha 3 integrin association. Strong CD151 association with integrin alpha 6 beta 1 also required the QRD(194-196) site and masked the TS151r epitope. For both alpha 3 and alpha 6 integrins, strong QRD/TS151r-dependent CD151 association occurred early in biosynthesis and involved alpha subunit precursor forms. In contrast, weaker associations of CD151 with itself, integrins, or other tetraspanins (Triton X-100-sensitive but Brij 96-resistant) were independent of the QRD/TS151r site, occurred late in biosynthesis, and involved mature integrin subunits. Presence of the CD151-QRD(194-196)-->INF mutant disrupted alpha 3 and alpha 6 integrin-dependent formation of a network of cellular cables by Cos7 or NIH3T3 cells on basement membrane Matrigel and markedly altered cell spreading. These results provide definitive evidence that strong lateral CD151-integrin association is functionally important, identify CD151 as a key player during alpha 3 and alpha 6 integrin-dependent matrix remodeling and cell spreading, and support a model of CD151 as a transmembrane linker between extracellular integrin domains and intracellular cytoskeleton/signaling molecules.

MeSH Terms
Animals Antigens, CD/metabolism Cell Adhesion/physiology Cells, Cultured Epitopes/metabolism Extracellular Space Humans Immunoblotting Integrin alpha3beta1/metabolism Integrin alpha6beta1/metabolism Mutagenesis, Site-Directed Octoxynol/chemistry Peptide Fragments/metabolism Plasmids Precipitin Tests Protein Binding Sequence Deletion Tetraspanin 24
Chemicals
Antigens, CD CD151 protein, human Epitopes Integrin alpha3beta1 Integrin alpha6beta1 Peptide Fragments Tetraspanin 24 Octoxynol
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kazarov Alexander R
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Yang Xiuwei
Stipp Christopher S
Sehgal Bantoo
Hemler Martin E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200204056
Published
2002-09-30
Pages
1299-309
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173251
Subset
IM
Grants
NCI NIH HHS · R01 CA042368 · United States
NCI NIH HHS · R01 CA086712 · United States
NCI NIH HHS · CA42368 · United States
NCI NIH HHS · CA86712 · United States
External Links
PubMed source DOI: 10.1083/jcb.200204056 PMC Full Text View journal details
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