title: Mammalian target of rapamycin complex 2 modulates αβTCR processing and surface expression during thymocyte development.
abstract: An efficient immune response relies on the presence of T cells expressing a functional TCR. Whereas the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls its surface expression is less known. In this study, we found that deletion of the mammalian target of rapamycin complex (mTORC) 2 component rictor at early stages of T cell development led to aberrant maturation and increased proteasomal degradation of nascent TCRs. Although CD127 expression became elevated, the levels of TCRs as well as CD4, CD8, CD69, Notch, and CD147 were significantly attenuated on the surface of rictor-deficient thymocytes. Diminished expression of these receptors led to suboptimal signaling, partial CD4(-)CD8(-) double-negative 4 (CD25(-)CD44(-)) proliferation, and CD4(+)CD8(+) double-positive activation as well as developmental blocks at the CD4(-)CD8(-) double-negative 3 (CD25(+)CD44(-)) and CD8-immature CD8(+) single-positive stages. Because CD147 glycosylation was also defective in SIN1-deficient fibroblasts, our findings suggest that mTORC2 is involved in the co/posttranslational processing of membrane receptors. Thus, mTORC2 impacts development via regulation of the quantity and quality of receptors important for cell differentiation.
authors: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854;
authors: Po-Chien
authors: PC
authors: Chou
authors: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854;
authors: Won Jun
authors: WJ
authors: Oh
authors: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854;
authors: Chang-Chih
authors: CC
authors: Wu
authors: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854;
authors: Joseph
authors: J
authors: Moloughney
authors: Biozentrum, University of Basel, CH 4056 Basel, Switzerland; and.
authors: Markus A
authors: MA
authors: Rüegg
authors: Biozentrum, University of Basel, CH 4056 Basel, Switzerland; and.
authors: Michael N
authors: MN
authors: Hall
authors: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ 08854; jacintes@rwjms.rutgers.edu guy.werlen@rutgers.edu.
authors: Estela
authors: E
authors: Jacinto
authors: Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 jacintes@rwjms.rutgers.edu guy.werlen@rutgers.edu.
authors: Guy
authors: G
authors: Werlen
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000172:deficiency / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology*; D021122:Protein Subunits / Q000172:deficiency / Q000502:physiology; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C525637:rictor protein, mouse; C546843:mTOR protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases