Interaction of Rab31 and OCRL-1 in oligodendrocytes: its role in transport of mannose 6-phosphate receptors.
Rab31, a protein that we cloned from an oligodendrocyte cDNA library, is required for transport of mannose 6-phosphate receptors (MPRs) from the trans-Golgi network (TGN) to endosomes and for Golgi/TGN organization. Here we extend the knowledge of the mechanism of action of Rab31 by demonstrating its interaction with OCRL-1, a ... phosphatidylinositol 4,5-diphosphate 5-phosphatase (PI(4,5)P(2) 5-phosphatase) that regulates the levels of PI(4,5)P(2) and PI(4)P, molecules involved in transport and Golgi/TGN organization. We show that Rab31 interacts with OCRL-1 in a yeast two-hybrid system, GST-Rab31 pull-down experiments, and coimmunoprecipitation of OCRL-1 using oligodendrocyte culture lysates. Rab31 and OCRL-1 colocalize in the TGN, post-TGN carriers, and endosomes. Cation-dependent MPR (CD-MPR) is sorted to OCRL-1-containing carriers, but CD63 and vesicular stomatitis virus G (VSVG) are not. siRNA-mediated depletion of endogenous Rab31 causes collapse of the TGN apparatus and markedly decreases the levels of OCRL-1 in the TGN and endosomes. Our observations indicate that the role of Rab31 in the Golgi/TGN structure and transport of MPRs depends on its capability to recruit OCRL-1 to domains of the TGN where the formation of carriers occurs. The importance of our observations is highlighted by the fact that mutation of OCRL-1 causes demyelination in humans.
Mesh Terms:
Animals, Antigens, CD, Brain, Cations, Cell Membrane, Cells, Cultured, Endosomes, HeLa Cells, Humans, Mice, Oligodendroglia, Phosphoric Monoester Hydrolases, Platelet Membrane Glycoproteins, Protein Binding, Protein Conformation, Rats, Receptor, IGF Type 2, Tetraspanin 30, rab GTP-Binding Proteins, trans-Golgi Network
Animals, Antigens, CD, Brain, Cations, Cell Membrane, Cells, Cultured, Endosomes, HeLa Cells, Humans, Mice, Oligodendroglia, Phosphoric Monoester Hydrolases, Platelet Membrane Glycoproteins, Protein Binding, Protein Conformation, Rats, Receptor, IGF Type 2, Tetraspanin 30, rab GTP-Binding Proteins, trans-Golgi Network
J. Neurosci. Res.
Date: Feb. 15, 2010
PubMed ID: 19795375
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