Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells.

Published

Journal Article

Linker for activation of T cells (LAT) is a dually palmitoylated transmembrane adaptor protein essential for T cell development and activation. However, whether LAT palmitoylation and/or lipid raft localization are required for its function is controversial. To address this question, we used a combination of biochemical, imaging, and genetic approaches, including LAT retrovirus-transduced mouse T cells and bone marrow chimeric mice. A nonpalmitoylated, non-lipid raft-residing mutant of transmembrane LAT could not reconstitute T cell development in bone marrow chimeric mice. This mutant was absent from the plasma membrane (PM) and was restricted mainly to the Golgi apparatus. A chimeric, nonpalmitoylated LAT protein consisting of the PM-targeting N-terminal sequence of Src kinase and the LAT cytoplasmic domain (Src-LAT) localized as a peripheral membrane protein in the PM, but outside lipid rafts. Nevertheless, Src-LAT restored T cell development and activation. Lastly, monopalmitoylation of LAT on Cys(26) (but not Cys(29)) was required and sufficient for its PM transport and function. Thus, the function of LAT in T cells requires its PM, but not raft, localization, even when expressed as a peripheral membrane protein. Furthermore, LAT palmitoylation functions primarily as a sorting signal required for its PM transport.

Full Text

Duke Authors

Cited Authors

  • Hundt, M; Harada, Y; De Giorgio, L; Tanimura, N; Zhang, W; Altman, A

Published Date

  • August 1, 2009

Published In

Volume / Issue

  • 183 / 3

Start / End Page

  • 1685 - 1694

PubMed ID

  • 19592663

Pubmed Central ID

  • 19592663

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0803921

Language

  • eng

Conference Location

  • United States