Ducharme Nicole A, Williams Janice A, Oztan Asli, Apodaca Gerard, Lapierre Lynne A, Goldenring James R
Vanderbilt Univ. School of Medicine, Dept. of Surgery, Epithelial Biology Program, 4160A MRB III, 465 21st St. S., Nashville, TN 37232-2733, USA.
Am J Physiol Cell Physiol. 2007 Sep;293(3):C1059-72. doi: 10.1152/ajpcell.00078.2007. Epub 2007 Jul 11.
Transcytosis through the apical recycling system of polarized cells is regulated by Rab11a and a series of Rab11a-interacting proteins. We have identified a point mutant in Rab11 family interacting protein 2 (Rab11-FIP2) that alters the function of Rab11a-containing trafficking systems. Rab11-FIP2(S229A/R413G) or Rab11-FIP2(R413G) cause the formation of a tubular cisternal structure containing Rab11a and decrease the rate of polymeric IgA transcytosis. The R413G mutation does not alter Rab11-FIP interactions with any known binding partners. Overexpression of Rab11-FIP2(S229A/R413G) alters the localization of a subpopulation of the apical membrane protein GP135. In contrast, Rab11-FIP2(129-512) alters the localization of early endosome protein EEA1. The distributions of both Rab11-FIP2(S229A/R413G) and Rab11-FIP2(129-512) were not dependent on the integrity of the microtubule cytoskeleton. The results indicate that Rab11-FIP2 regulates trafficking at multiple points within the apical recycling system of polarized cells.
通过极化细胞的顶端循环系统进行的转胞吞作用受Rab11a和一系列与Rab11a相互作用的蛋白质调控。我们在Rab11家族相互作用蛋白2(Rab11-FIP2)中鉴定出一个点突变,该突变改变了含Rab11a的运输系统的功能。Rab11-FIP2(S229A/R413G)或Rab11-FIP2(R413G)导致形成含有Rab11a的管状池状结构,并降低聚合IgA转胞吞作用的速率。R413G突变不会改变Rab11-FIP与任何已知结合伴侣的相互作用。Rab11-FIP2(S229A/R413G)的过表达改变了顶端膜蛋白GP135亚群的定位。相反,Rab11-FIP2(129-512)改变了早期内体蛋白EEA1的定位。Rab11-FIP2(S229A/R413G)和Rab11-FIP2(129-512)的分布均不依赖于微管细胞骨架的完整性。结果表明,Rab11-FIP2在极化细胞顶端循环系统内的多个点调节运输。