UNC119 inhibits dynamin and dynamin-dependent endocytic processes.
Unc119 is an adapter signaling molecule, which regulates activation of tyrosine kinases in T cells, eosinophils and fibroblasts. It plays an important role in the photoreceptor synapses of the retina. Recently, we have shown that it inhibits bacterial uptake through macropinocytosis. In this paper we demonstrate a role for Unc119 in clathrin- and caveolae-based endocytosis as well as macropinocytosis. Depletion of Unc119 in fibroblasts increases, whereas overexpression inhibits uptake of transferrin, FM4-64, albumin, viruses, and ligand-coated beads. Physiological stimuli that upregulate the expression of Unc119 also inhibits endocytosis. Unc119 has the opposite effect on cholera toxin B uptake, which represents a clathrin- and dynamin-independent endocytic process. Unc119 interacts with dynamin, a key effector molecule of many endocytic processes. More importantly, Unc119 inhibits the GTPase activity of dynamin. Binding of Unc119 to dynamin decreases the association with its binding partner amphiphysin, a known regulator of dynamin activation. Thus, Unc119 regulates various endocytic pathways through dynamin and sets a threshold point for vesicular trafficking.
Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
Zunayet
Z
Karim
Ramarao
R
Vepachedu
Magdalena
M
Gorska
Rafeul
R
Alam
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding
D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; C489115:Unc119 protein, mouse; C075637:amphiphysin; D020558:GTP Phosphohydrolases; D034281:Dynamins