Palmitoylation of tetraspanin proteins: modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology

Mol Biol Cell. 2002 Mar;13(3):767-81. doi: 10.1091/mbc.01-05-0275.


Here we demonstrate that multiple tetraspanin (transmembrane 4 superfamily) proteins are palmitoylated, in either the Golgi or a post-Golgi compartment. Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites. Simultaneous mutations of C11, C15, C242, and C243 (each to serine) eliminated >90% of CD151 palmitoylation. Notably, palmitoylation had minimal influence on the density of tetraspanin protein complexes, did not promote tetraspanin localization into detergent-resistant microdomains, and was not required for CD151-alpha 3 beta 1 integrin association. However, the CD151 tetra mutant showed markedly diminished associations with other cell surface proteins, including other transmembrane 4 superfamily proteins (CD9, CD63). Thus, palmitoylation may be critical for assembly of the large network of cell surface tetraspanin-protein interactions, sometimes called the "tetraspanin web." Also, compared with wild-type CD151, the tetra mutant was much more diffusely distributed and showed markedly diminished stability during biosynthesis. Finally, expression of the tetra-CD151 mutant profoundly altered alpha 3 integrin-deficient kidney epithelial cells, such that they converted from a dispersed, elongated morphology to an epithelium-like cobblestone clustering. These results point to novel biochemical and biological functions for tetraspanin palmitoylation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Biological Transport / physiology
  • Brefeldin A / pharmacology
  • Cell Line
  • Cell Size*
  • Green Fluorescent Proteins
  • Humans
  • Indicators and Reagents / metabolism
  • Integrin alpha3beta1 / metabolism*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Palmitates / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Tetraspanin 24


  • Antigens, CD
  • CD151 protein, human
  • Indicators and Reagents
  • Integrin alpha3beta1
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Palmitates
  • Protein Synthesis Inhibitors
  • Recombinant Fusion Proteins
  • Tetraspanin 24
  • Green Fluorescent Proteins
  • Brefeldin A