Rab8 Regulates Basolateral Secretory, But Not Recycling, Traffic at the Recycling Endosome
- 1 May 2008
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 19 (5), 2059-2068
- https://doi.org/10.1091/mbc.e07-09-0902
Abstract
Rab8 is a monomeric GTPase that regulates the delivery of newly synthesized proteins to the basolateral surface in polarized epithelial cells. Recent publications have demonstrated that basolateral proteins interacting with the μ1-B clathrin adapter subunit pass through the recycling endosome (RE) en route from the TGN to the plasma membrane. Because Rab8 interacts with these basolateral proteins, these findings raise the question of whether Rab8 acts before, at, or after the RE. We find that Rab8 overexpression during the formation of polarity in MDCK cells, disrupts polarization of the cell, explaining how Rab8 mutants can disrupt basolateral endocytic and secretory traffic. However, once cells are polarized, Rab8 mutants cause mis-sorting of newly synthesized basolateral proteins such as VSV-G to the apical surface, but do not cause mis-sorting of membrane proteins already at the cell surface or in the endocytic recycling pathway. Enzymatic ablation of the RE also prevents traffic from the TGN from reaching the RE and similarly results in mis-sorting of newly synthesized VSV-G. We conclude that Rab8 regulates biosynthetic traffic through REs to the plasma membrane, but not trafficking of endocytic cargo through the RE. The data are consistent with a model in which Rab8 functions in regulating the delivery of TGN-derived cargo to REs.Keywords
This publication has 50 references indexed in Scilit:
- Differential involvement of endocytic compartments in the biosynthetic traffic of apical proteinsThe EMBO Journal, 2007
- Myosin Vb Interacts with Rab8a on a Tubular Network Containing EHD1 and EHD3Molecular Biology of the Cell, 2007
- Recycling Endosomes of Polarized Epithelial Cells Actively Sort Apical and Basolateral Cargos into Separate SubdomainsMolecular Biology of the Cell, 2007
- AP1B sorts basolateral proteins in recycling and biosynthetic routes of MDCK cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Characterization of the Rab8-specific membrane traffic route linked to protrusion formationJournal of Cell Science, 2006
- Large-Scale Profiling of Rab GTPase Trafficking Networks: The MembromeMolecular Biology of the Cell, 2005
- The exocyst localizes to the primary cilium in MDCK cellsBiochemical and Biophysical Research Communications, 2004
- Actin Dependence of Polarized Receptor Recycling in Madin-Darby Canine Kidney Cell EndosomesMolecular Biology of the Cell, 2002
- Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p.The Journal of cell biology, 1993
- Relations between the intracellular pathways of the receptors for transferrin, asialoglycoprotein, and mannose 6-phosphate in human hepatoma cells.The Journal of cell biology, 1989