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The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.

Publication ,  Journal Article
McLeod, IX; Zhou, X; Li, Q-J; Wang, F; He, Y-W
Published in: J Immunol
November 15, 2011

IL-7Rα-mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. In this paper, we show that Vps34, the class III PI3K, plays a critical role in proper IL-7Rα intracellular trafficking. Mice lacking Vps34 in T lymphocytes had a severely reduced T lymphocyte compartment. Vps34-deficient T lymphocytes exhibit increased death and reduced IL-7Rα surface expression, although three major forms of autophagy remain intact. Intracellular IL-7Rα in normal T lymphocytes at steady state is trafficked through either early endosome/multivesicular bodies to the late endosome-Golgi for surface expression or to the lysosome for degradation. However, Vps34-deficient T cells have mislocalized intracellular Eea1, HGF-regulated tyrosine kinase substrate, and Vps36 protein levels, the combined consequence of which is the inability to mobilize internalized IL-7Rα into the retromer pathway for surface display. Our studies reveal that Vps34, though dispensable for autophagy induction, is a critical regulator of naive T cell homeostasis, modulating IL-7Rα trafficking, signaling, and recycling.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2011

Volume

187

Issue

10

Start / End Page

5051 / 5061

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Interleukin-7
  • Proto-Oncogene Proteins
  • Protein Transport
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Membrane Proteins
 

Citation

APA
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ICMJE
MLA
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McLeod, I. X., Zhou, X., Li, Q.-J., Wang, F., & He, Y.-W. (2011). The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression. J Immunol, 187(10), 5051–5061. https://doi.org/10.4049/jimmunol.1100710
McLeod, Ian X., Xiang Zhou, Qi-Jing Li, Fan Wang, and You-Wen He. “The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.J Immunol 187, no. 10 (November 15, 2011): 5051–61. https://doi.org/10.4049/jimmunol.1100710.
McLeod IX, Zhou X, Li Q-J, Wang F, He Y-W. The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression. J Immunol. 2011 Nov 15;187(10):5051–61.
McLeod, Ian X., et al. “The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.J Immunol, vol. 187, no. 10, Nov. 2011, pp. 5051–61. Pubmed, doi:10.4049/jimmunol.1100710.
McLeod IX, Zhou X, Li Q-J, Wang F, He Y-W. The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression. J Immunol. 2011 Nov 15;187(10):5051–5061.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2011

Volume

187

Issue

10

Start / End Page

5051 / 5061

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Signal Transduction
  • Receptors, Interleukin-7
  • Proto-Oncogene Proteins
  • Protein Transport
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Membrane Proteins