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

Xiuwei Yang, Christoph Claas, Stine Kathrein Kraeft, Lan Bo Chen, Zemin Wang, Jordan A. Kreidberg, Martin E. Hemler

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

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 CID151-α3β1 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 α3 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.

Original languageEnglish
Pages (from-to)767-781
Number of pages15
JournalMolecular Biology of the Cell
Volume13
Issue number3
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Palmitoylation of tetraspanin proteins: Modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology'. Together they form a unique fingerprint.

Cite this