A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes.
Rab11 is a GTPase that regulates endosomal trafficking to apical plasma membrane domains in polarized epithelial cells. We report the identification of a novel Rab11 effector, Rip11. Rip11 is enriched in polarized epithelial cells where, like Rab11, it is localized to subapical recycling endosomes (ARE) and the apical plasma membrane. Using various transport assays, we demonstrate that Rip11 is important for protein trafficking from ARE to the apical plasma membrane. Rip11 is recruited to ARE by binding to Rab11 as well as through a Mg(2+)-dependent interaction of its C2 domain with neutral phospholipids. The association of Rip11 with membranes is regulated by a phosphorylation and dephosphorylation cycle. We propose a model whereby the Rab11/Rip 11 complex regulates vesicle targeting from the ARE.
Prekeris
R
R
Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Klumperman
J
J
Scheller
R H
RH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000737:chemistry / Q000648:ultrastructure; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008854:Microscopy, Electron; D024101:Mitochondrial Proteins; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010743:Phospholipids; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C485422:RAB11FIP5 protein, human