Uncoordinated 119 protein controls trafficking of Lck via the Rab11 endosome and is critical for immunological synapse formation.
The activation of T cells through the TCR is essential for development of the adaptive immune response. TCR does not have any enzymatic activity and relies on the plasma membrane-associated lymphocyte-specific protein tyrosine kinase (Lck) for initiation of signaling. Here we uncover a mechanism that is responsible for plasma membrane targeting of Lck. We show that Lck is transported to the membrane via a specific endosomal compartment. The transport depends on the adaptor protein Uncoordinated 119 (Unc119), on the GTPase rat brain 11 (Rab11), and on the actin cytoskeleton. Unc119 regulates the activation of Rab11. Consequently, Unc119 orchestrates the recruitment of the actin-based motor protein, myosin 5B, and the organization of multiprotein complexes on endosomes. The Unc119-regulated pathway is essential for immunological synapse formation and T cell activation.
Gorska
Magdalena M
MM
Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
Liang
Qiaoling
Q
Karim
Zunayet
Z
Alam
Rafeul
R
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D003599:Cytoskeleton; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes; D009218:Myosins / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046912:Multiprotein Complexes; D009218:Myosins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C101826:Myo5b protein, rat; C098032:UNC119 protein, human; C489115:Unc119 protein, mouse