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

Publication ,  Journal Article
Hundt, M; Harada, Y; De Giorgio, L; Tanimura, N; Zhang, W; Altman, A
Published in: J Immunol
August 1, 2009

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.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 1, 2009

Volume

183

Issue

3

Start / End Page

1685 / 1694

Location

United States

Related Subject Headings

  • src-Family Kinases
  • T-Lymphocytes
  • Signal Transduction
  • Protein Transport
  • Phosphoproteins
  • Mice
  • Membrane Proteins
  • Membrane Microdomains
  • Lipoylation
  • Immunology
 

Citation

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MLA
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Hundt, M., Harada, Y., De Giorgio, L., Tanimura, N., Zhang, W., & Altman, A. (2009). Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells. J Immunol, 183(3), 1685–1694. https://doi.org/10.4049/jimmunol.0803921
Hundt, Matthias, Yohsuke Harada, Lauren De Giorgio, Natsuko Tanimura, Weiguo Zhang, and Amnon Altman. “Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells.J Immunol 183, no. 3 (August 1, 2009): 1685–94. https://doi.org/10.4049/jimmunol.0803921.
Hundt M, Harada Y, De Giorgio L, Tanimura N, Zhang W, Altman A. Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells. J Immunol. 2009 Aug 1;183(3):1685–94.
Hundt, Matthias, et al. “Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells.J Immunol, vol. 183, no. 3, Aug. 2009, pp. 1685–94. Pubmed, doi:10.4049/jimmunol.0803921.
Hundt M, Harada Y, De Giorgio L, Tanimura N, Zhang W, Altman A. Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells. J Immunol. 2009 Aug 1;183(3):1685–1694.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 1, 2009

Volume

183

Issue

3

Start / End Page

1685 / 1694

Location

United States

Related Subject Headings

  • src-Family Kinases
  • T-Lymphocytes
  • Signal Transduction
  • Protein Transport
  • Phosphoproteins
  • Mice
  • Membrane Proteins
  • Membrane Microdomains
  • Lipoylation
  • Immunology