Karim Zunayet, Vepachedu Ramarao, Gorska Magdalena, Alam Rafeul
Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
Cell Signal. 2010 Jan;22(1):128-37. doi: 10.1016/j.cellsig.2009.09.022. Epub 2009 Sep 23.
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.
Unc119是一种衔接信号分子，可调节T细胞、嗜酸性粒细胞和成纤维细胞中酪氨酸激酶的激活。它在视网膜的光感受器突触中起重要作用。最近，我们发现它可通过巨胞饮作用抑制细菌摄取。在本文中，我们证明了Unc119在网格蛋白介导的内吞作用、小窝蛋白介导的内吞作用以及巨胞饮作用中发挥作用。成纤维细胞中Unc119的缺失会增加转铁蛋白、FM4-64、白蛋白、病毒和配体包被珠子的摄取，而其过表达则会抑制这些摄取。上调Unc119表达的生理刺激也会抑制内吞作用。Unc119对霍乱毒素B的摄取有相反的作用，霍乱毒素B的摄取代表一种不依赖网格蛋白和发动蛋白的内吞过程。Unc119与发动蛋白相互作用，发动蛋白是许多内吞过程的关键效应分子。更重要的是，Unc119抑制发动蛋白的GTP酶活性。Unc119与发动蛋白结合会减少其与结合伴侣发动蛋白激活的已知调节剂 amphiphysin的结合。因此，Unc119通过发动蛋白调节各种内吞途径，并为囊泡运输设定一个阈值点。
