| First Author | McLeod IX | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 10 | Pages | 5051-61 |
| PubMed ID | 22021616 | Mgi Jnum | J:179594 |
| Mgi Id | MGI:5302742 | Doi | 10.4049/jimmunol.1100710 |
| Citation | McLeod IX, et al. (2011) The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Ralpha surface expression. J Immunol 187(10):5051-61 |
| abstractText | IL-7Ralpha-mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Ralpha is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Ralpha trafficking is regulated is unclear. In this paper, we show that Vps34, the class III PI3K, plays a critical role in proper IL-7Ralpha 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-7Ralpha surface expression, although three major forms of autophagy remain intact. Intracellular IL-7Ralpha 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-7Ralpha 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-7Ralpha trafficking, signaling, and recycling. |
