Palmitoylation supports assembly and function of integrin-tetraspanin complexes

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

doi:10.1083/jcb.200404100

Back

Palmitoylation supports assembly and function of integrin-tetraspanin complexes

Journal article

Open access

Peer reviewed

Palmitoylation supports assembly and function of integrin-tetraspanin complexes

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

The Journal of cell biology, Vol.167(6), pp.1231-1240

12/20/2004

DOI: 10.1083/jcb.200404100

PMCID: PMC2172609

PMID: 15611341

Files and links (1)

url

https://doi.org/10.1083/jcb.200404100View

Published (Version of record) Open Access

Abstract

As observed previously, tetraspanin palmitoylation promotes tetraspanin microdomain assembly. Here, we show that palmitoylated integrins (alpha3, alpha6, and beta4 subunits) and tetraspanins (CD9, CD81, and CD63) coexist in substantially overlapping complexes. Removal of beta4 palmitoylation sites markedly impaired cell spreading and signaling through p130Cas on laminin substrate. Also in palmitoylation-deficient beta4, secondary associations with tetraspanins (CD9, CD81, and CD63) were diminished and cell surface CD9 clustering was decreased, whereas core alpha6beta4-CD151 complex formation was unaltered. There is also a functional connection between CD9 and beta4 integrins, as evidenced by anti-CD9 antibody effects on beta4-dependent cell spreading. Notably, beta4 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 beta4 (and of the closely associated tetraspanin CD151) promotes CD151-alpha6beta4 incorporation into a network of secondary tetraspanin interactions (with CD9, CD81, CD63, etc.), which provides a novel framework for functional regulation.

Cell Line

Palmitic Acid - metabolism

Membrane Glycoproteins - metabolism

Membrane Microdomains - metabolism

Humans

Integrins - metabolism

Protein Subunits - metabolism

Antigens, CD - metabolism

Integrin beta3 - metabolism

Animals

src-Family Kinases - metabolism

Membrane Proteins - metabolism

Tetraspanin-29

Macromolecular Substances - metabolism

Receptors, Growth Factor - metabolism

Details

Title: Subtitle: Palmitoylation supports assembly and function of integrin-tetraspanin complexes
Creators: Xiuwei Yang - Dana-Farber Cancer Institute
Oleg V Kovalenko
Wei Tang - Dana-Farber Cancer Institute
Christoph Claas
Christopher S Stipp
Martin E Hemler
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.167(6), pp.1231-1240
DOI: 10.1083/jcb.200404100
PMID: 15611341
PMCID: PMC2172609
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Publisher: United States
Grant note: R01 CA086712 / NCI NIH HHS R01 CA042368 / NCI NIH HHS CA42368 / NCI NIH HHS CA86712 / NCI NIH HHS
Language: English
Date published: 12/20/2004
Academic Unit: Molecular Physiology and Biophysics; Biology
Record Identifier: 9983991996502771

Metrics

27 Record Views

180 Times Cited - Web of Science

See more details