Premium
Tetraspanin CD151 is Required for Both α3 and α6 Integrin Function
Author(s) -
Zevian Shannin,
Winterwood Nicole,
Meland Marit,
Stipp Chris
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.895.7
Subject(s) - tetraspanin , biology , phenotype , laminin , mutant , microbiology and biotechnology , integrin , palmitoylation , gene silencing , cell adhesion , motility , cancer research , genetics , cell , gene , extracellular matrix , biochemistry , cysteine , enzyme
A benchmark characteristic of malignancy is an invasive phenotype often associated with tumor cell motility. We, and others, have described a critical role for tetraspanin CD151 in α3β1‐dependent tumor cell responses to laminin‐332. When CD151 is silenced, carcinoma cells exhibit impaired adhesion and migration on laminin‐332, phenotypes that can be reversed upon re‐expression of CD151. We have now begun to use this silencing and reconstitution system to explore the domains in CD151 required for its ability to promote α3β1 function. Mutation of a QRD motif in the EC2 domain of CD151 abolished CD151 association with α3β1 under harsh detergent conditions, as previously described. Surprisingly, however, the QRD mutation did not abolish CD151 association with α3β1 under moderate, Brij detergent conditions. Moreover, in experiments to date, the CD151 QRD mutant appears fully capable of rescuing α3β1‐dependent adhesion and migration. More severe EC2 mutations, which abolish α3β1 association even under mild conditions, cannot rescue the phenotypes of CD151‐silenced cells. In addition, CD151 palmitoylation sites are critical for CD151’s ability to link α3β1 to other tetraspanins, and for its ability to reverse the phenotypes of CD151‐silenced cells. Interestingly, palmitoylation mutants, but not severe EC2 mutants, are able to resist detachment when allowed to grow and spread on plates for at least 24 hours. Collectively, these data show that CD151’s ability to associate with its integrin partners and with other tetraspanins are both critical for its functions in adhesion and motility, and support a model in which one of CD151’s most important functions is to act as linker to target its integrin partners to tetraspanin microdomains. This work was supported by an American Cancer Society Research Scholar Award.