Journal article
Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin
The Journal of biological chemistry, Vol.286(9), pp.7496-7506
03/04/2011
DOI: 10.1074/jbc.M110.173583
PMCID: PMC3045005
PMID: 21193415
Abstract
The basement membrane protein laminin-332 (laminin-5) mediates both stable cell adhesion and rapid cell migration and thus has the potential to either restrain or promote tumor cell metastasis. The major cellular receptors for laminin-332 are integrin α3β1, which mediates rapid tumor cell migration, and integrin α6β4, which often mediates stable cell attachment. Tetraspanin protein CD151 interacts directly with both α3β1 and α6β4 integrins and with other tetraspanins, thereby promoting α3β1 and α6β4 association with tetraspanin-enriched microdomains on the cell surface. To explore the possibility of selectively modulating tumor cell responses to laminin-332, we re-expressed a series of CD151 mutants in epidermoid carcinoma cells with near total, RNAi-mediated silencing of endogenous CD151. The interactions of CD151 with its integrin partners or its interactions with other tetraspanins were selectively disrupted by specific mutations in the CD151 large extracellular loop (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151-integrin association and CD151-tetraspanin association were both important for α3β1 integrin-dependent initial adhesion and rapid migration on laminin-332. Remarkably, however, only CD151-integrin association was required for stable, α6β4 integrin-dependent cell attachment on laminin-332. In addition, we found that a QRD amino acid motif in the CD151 EC2 domain, which had been thought to be crucial for CD151-integrin interaction, is not essential for CD151-integrin association or for the ability of CD151 to promote several different integrin functions. These new data suggest potential strategies for selectively modulating migratory cell responses to laminin-332, while leaving stable cell attachment on laminin-332 intact.
Details
- Title: Subtitle
- Structure-Function Analysis of Tetraspanin CD151 Reveals Distinct Requirements for Tumor Cell Behaviors Mediated by α3β1 versus α6β4 Integrin
- Creators
- Shannin Zevian - Departments of BiologyNicole E Winterwood - Departments of BiologyChristopher S Stipp - Departments of Biology
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.286(9), pp.7496-7506
- DOI
- 10.1074/jbc.M110.173583
- PMID
- 21193415
- PMCID
- PMC3045005
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/04/2011
- Academic Unit
- Molecular Physiology and Biophysics; Biology
- Record Identifier
- 9984217416102771
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