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.
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20 December 2004
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December 20 2004
Palmitoylation supports assembly and function of integrin–tetraspanin complexes
Xiuwei Yang,
Xiuwei Yang
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Oleg V. Kovalenko,
Oleg V. Kovalenko
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Wei Tang,
Wei Tang
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Christoph Claas,
Christoph Claas
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Christopher S. Stipp,
Christopher S. Stipp
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Martin E. Hemler
Martin E. Hemler
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
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Xiuwei Yang
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Oleg V. Kovalenko
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Wei Tang
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Christoph Claas
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Christopher S. Stipp
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Martin E. Hemler
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Correspondence to Martin E. Hemler: [email protected]
Abbreviations used in this paper: EGFR, EGF receptor; TEM, tetraspanin-enriched microdomain.
Received:
April 16 2004
Accepted:
November 07 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 167 (6): 1231–1240.
Article history
Received:
April 16 2004
Accepted:
November 07 2004
Citation
Xiuwei Yang, Oleg V. Kovalenko, Wei Tang, Christoph Claas, Christopher S. Stipp, Martin E. Hemler; Palmitoylation supports assembly and function of integrin–tetraspanin complexes . J Cell Biol 20 December 2004; 167 (6): 1231–1240. doi: https://doi.org/10.1083/jcb.200404100
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