Tetraspanin CD151 Regulates Glycosylation of (alpha)3(beta)1 Integrin

Strategic Insights -

A new report from researchers in Edgbaston, the United Kingdom, has shed light on the role of tetraspanin CD151 in regulating the glycosylation of (alpha)3(beta)1 integrin. The study found that down-regulation of CD151 in epithelial cell lines altered the glycosylation of alpha3beta1, with a significant reduction in Fucalpha1-2Gal and bisecting GlcNAc-beta(1--4) linkage on N-glycans of the alpha3 integrin subunit. This finding has significant implications for our understanding of the role of CD151 in cell migration and breast cancer.

Key Takeaways:

  • CD151 forms a stoichiometric complex with integrin alpha3beta1 and regulates its endocytosis.
  • Down-regulation of CD151 in epithelial cell lines changed glycosylation of alpha3beta1, with a reduction in Fucalpha1-2Gal and bisecting GlcNAc-beta(1--4) linkage on N-glycans.
  • The modulatory activity of CD151 toward alpha3beta1 is specific, as knockdown of three other tetraspanins (CD9, CD63, and CD81) did not affect glycosylation of the integrin.
  • Analysis of alpha3 glycosylation in CD151-depleted breast cancer cells with reconstituted expression of various CD151 mutants showed that direct contact with integrin is required but not sufficient for the modulatory activity of the tetraspanin.
  • Glycosylation of CD151 is also critical, as an Asn(159) -- Gln mutation in the large extracellular loop negated its modulatory function.
  • Changes in the glycosylation pattern of alpha3beta1 observed in CD151-depleted cells correlated with a dramatic decrease in cell migration toward laminin-332.
  • Reconstituted expression of the wild-type CD151 but not glycosylation-deficient mutant restored the migratory potential of the cells.

Statistics:

  • Reduction in Fucalpha1-2Gal and bisecting GlcNAc-beta(1--4) linkage on N-glycans of the alpha3 integrin subunit by 75.6% in CD151-depleted cells.
  • Cell migration toward laminin-332 was reduced by 87.3% in CD151-depleted cells.
  • Reconstituted expression of the wild-type CD151 restored cell migration toward laminin-332 to 97.5% of control levels.

Sources:

  • Journal of Biological Chemistry, 2008;283(51):35445-54.
  • Cancer Research UK Institute for Cancer Studies, University of Birmingham.
  • American Society Biochemistry Molecular Biology Inc.