Rab11-FIP2 regulates differentiable steps in transcytosis.
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.
Ducharme
Nicole A
NA
Vanderbilt Univ. School of Medicine, Dept. of Surgery, Epithelial Biology Program, 4160A MRB III, 465 21st St. S., Nashville, TN 37232-2733, USA. jim.goldenring@vanderbilt.edu
Williams
Janice A
JA
Oztan
Asli
A
Apodaca
Gerard
G
Lapierre
Lynne A
LA
Goldenring
James R
JR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D004285:Dogs; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D021381:Protein Transport / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins
D002352:Carrier Proteins; C120700:EHD1 protein, human; C406447:EHD3 protein, human; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; C463963:RAB11FIP2 protein, human; D020691:rab GTP-Binding Proteins