Morton Penny E, Hicks Alexander, Nastos Theodoros, Santis George, Parsons Maddy
1] Division of Asthma, Allergy & Lung Biology, King's College London, 5th Floor Tower Wing, Guy's Hospital Campus, London, United Kingdom [2] Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London, United Kingdom.
Sci Rep. 2013 Oct 7;3:2889. doi: 10.1038/srep02889.
CAR (Coxsackie and Adenovirus Receptor) is the primary docking receptor for typeB coxsackie viruses and subgroup C adenoviruses. CAR is a member of the JAM family of adhesion receptors and is located to both tight and adherens junctions between epithelial cells where it can assemble adhesive contacts through homodimerisation in trans. However, the role of CAR in controlling epithelial junction dynamics remains poorly understood. Here we demonstrate that levels of CAR in human epithelial cells play a key role in determining epithelial cell adhesion through control of E-cadherin stability at cell-cell junctions. Mechanistically, we show that CAR is phosphorylated within the C-terminus by PKCδ and that this in turn controls Src-dependent endocytosis of E-cadherin at cell junctions. This data demonstrates a novel role for CAR in regulating epithelial homeostasis.
柯萨奇病毒和腺病毒受体（CAR）是B型柯萨奇病毒和C亚组腺病毒的主要对接受体。CAR是JAM家族黏附受体的成员，位于上皮细胞之间的紧密连接和黏着连接部位，在那里它可以通过反式同源二聚化形成黏附接触。然而，CAR在控制上皮连接动态方面的作用仍知之甚少。在这里，我们证明人类上皮细胞中CAR的水平通过控制细胞间连接处E-钙黏蛋白的稳定性，在决定上皮细胞黏附中起关键作用。从机制上讲，我们表明CAR在C末端被蛋白激酶Cδ（PKCδ）磷酸化，进而控制细胞连接处E-钙黏蛋白的Src依赖性内吞作用。这些数据证明了CAR在调节上皮稳态中的新作用。
