Complexes of tetraspanins with integrins: more than meets the eye

J Cell Sci. 2001 Dec;114(Pt 23):4143-51. doi: 10.1242/jcs.114.23.4143.


The transmembrane proteins of the tetraspanin superfamily are implicated in a diverse range of biological phenomena, including cell motility, metastasis, cell proliferation and differentiation. The tetraspanins are associated with adhesion receptors of the integrin family and regulate integrin-dependent cell migration. In cells attached to the extracellular matrix, the integrin-tetraspanin adhesion complexes are clustered into a distinct type of adhesion structure at the cell periphery. Various tetraspanins are associated with phosphatidylinositol 4-kinase and protein kinase C isoforms, and they may facilitate assembly of signalling complexes by tethering these enzymes to integrin heterodimers. At the plasma membrane, integrin-tetraspanin signalling complexes are partitioned into specific microdomains proximal to cholesterol-rich lipid rafts. A substantial fraction of tetraspanins colocalise with integrins in various intracellular vesicular compartments. It is proposed that tetraspanins can influence cell migration by one of the following mechanisms: (1) modulation of integrin signalling; (2) compartmentalisation of integrins on the cell surface; or (3) direction of intracellular trafficking and recycling of integrins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Humans
  • Integrins / metabolism*
  • Membrane Microdomains / metabolism
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Signal Transduction
  • Tetraspanins


  • Integrins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TSPAN2 protein, human
  • TSPAN7 protein, human
  • Tetraspanins