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Am J Physiol Cell Physiol 293: C1059-C1072, 2007. First published July 11, 2007; doi:10.1152/ajpcell.00078.2007
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PROTEIN AND VESICLE TRAFFICKING, CYTOSKELETON

Rab11-FIP2 regulates differentiable steps in transcytosis

Nicole A. Ducharme,1 Janice A. Williams,1 Asli Oztan,2 Gerard Apodaca,2 Lynne A. Lapierre,1 and James R. Goldenring1

1Departments of Surgery and Cell and Developmental Biology, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center and the Nashville Veterans Affairs Medical Center, Nashville, Tennessee; and 2Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 22 February 2007 ; accepted in final form 22 June 2007

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.

Rab11a; immunoglobulin A; trafficking; apical recycling; GP135; early endosome; EEA1; Eps15 homology domain


Address for reprint requests and other correspondence: J. R. Goldenring, Vanderbilt Univ. School of Medicine, Dept. of Surgery, Epithelial Biology Program, 4160A MRB III, 465 21st St. S., Nashville, TN 37232-2733 (e-mail: jim.goldenring{at}vanderbilt.edu)




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[Abstract] [Full Text] [PDF]


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