Palmitoylation supports assembly and function of integrin-tetraspanin complexes

Xiuwei Yang, Oleg V. Kovalenko, Wei Tang, Christoph Claas, Christopher S. Stipp, Martin E. Hemler

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

As observed previously, tetraspanin palmitoylation promotes tetraspanin microdomain assembly. Here, we show that palmitoylated integrins (α3, α6, and β4 subunits) and tetraspanins (CD9, CD81, and CD63) coexist in substantially overlapping complexes. Removal of β4 palmitoylation sites markedly impaired cell spreading and signaling through p130Cas on laminin substrate. Also in palmitoylation-deficient β4, secondary associations with tetraspanins (CD9, CD81, and CD63) were diminished and cell surface CD9 clustering was decreased, whereas core α6β4-CD151 complex formation was unaltered. There is also a functional connection between CD9 and β4 integrins, as evidenced by anti-CD9 antibody effects on β4-dependent cell spreading. Notably, β4 palmitoylation neither increased localization into "light membrane" fractions of sucrose gradients nor decreased solubility in nonionic detergents-hence it does not promote lipid raft association. Instead, palmitoylation of β4 (and of the closely associated tetraspanin CD151) promotes CD151-α6β4 incorporation into a network of secondary tetraspanin interactions (with CD9, CD81, CD63, etc.), which provides a novel framework for functional regulation.

Original languageEnglish
Pages (from-to)1231-1240
Number of pages10
JournalJournal of Cell Biology
Volume167
Issue number6
DOIs
StatePublished - Dec 20 2004

ASJC Scopus subject areas

  • Cell Biology

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