Institute of Molecular Medicine, Division of Pathobiochemistry, Martin-Luther-University Halle, Hollystrasse 1, 06114 Halle, Germany.
J Cell Sci. 2014 Jan 1;127(Pt 1):60-71. doi: 10.1242/jcs.132266. Epub 2013 Oct 25.
p0071 is an intercellular junction protein of the p120 catenin family. We have identified Rab11a as a novel interaction partner of p0071. p0071 interacted preferentially with active Rab11a. Knockdown experiments revealed an interdependent regulation of both proteins. On the one hand, p0071 depletion induced a perinuclear accumulation of Rab11, suggesting a role of p0071 in the anterograde transport of Rab11 from the pericentrosomal region to the plasma membrane but not in retrograde transport. p0071 as well as Rab11 depletion increased transferrin receptor recycling indicating that p0071-induced Rab11 mislocalization interfered with Rab11 function and shifted recycling from the slow Rab11-dependent pathway to the fast Rab4-dependent pathway. When p0071 or Rab11 depletion was combined with a Rab4 knockdown the effect was reversed. On the other hand, Rab11a depletion increased p0071 recycling to cell contacts thereby identifying p0071 as a Rab11 cargo protein. This correlated with increased intercellular adhesion. Thus, we propose that p0071 has a key role in regulating recycling through the Rab11-dependent perinuclear recycling compartment, and links the regulation of adherens junctions to recycling to allow dynamic modulation of intercellular adhesion.
p0071 是细胞间连接蛋白 p120 连环蛋白家族的一员。我们已经确定 Rab11a 是 p0071 的一个新的相互作用伙伴。p0071 与活性 Rab11a 优先相互作用。敲低实验显示这两种蛋白质相互依存调节。一方面,p0071 的耗竭诱导 Rab11 的核周聚集,表明 p0071 在 Rab11 从中心体周围区域到质膜的正向运输中起作用,但不在逆行运输中起作用。p0071 以及 Rab11 的耗竭增加了转铁蛋白受体的回收,表明 p0071 诱导的 Rab11 定位错误干扰了 Rab11 的功能,并将回收从慢 Rab11 依赖途径转移到快 Rab4 依赖途径。当 p0071 或 Rab11 的耗竭与 Rab4 的敲低结合时,效果会逆转。另一方面,Rab11a 的耗竭增加了 p0071 向细胞接触的循环,从而将 p0071 鉴定为 Rab11 的货物蛋白。这与细胞间黏附的增加有关。因此,我们提出 p0071 在通过 Rab11 依赖性核周循环隔室调节回收方面起着关键作用,并将黏附连接的调节与回收联系起来,以允许细胞间黏附的动态调节。