title: Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6) is regulated by small GTPase Rab1B in the early secretory and autophagic pathways.
abstract: A large family of myotubularin phosphatases dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, which are known to play important roles in vesicular trafficking and autophagy. The family is composed of 16 members, and understanding their regulatory mechanisms is important to understand their functions and related genetic diseases. We prepared anti-myotubularin-related protein 6 (MTMR6) monoclonal antibody and used it to study the regulatory mechanism of MTMR6. Endogenous MTMR6 was present in the cytoplasm and was condensed in the perinuclear region in a microtubule-dependent manner. MTMR6 preferentially interacted with GDP-bound Rab1B via the GRAM domain and partly overlapped with Rab1B in the pericentrosomal and peri-Golgi regions in normal rat kidney cells. Overexpression of GDP-bound Rab1B and the reduction of Rab1B disrupted the localization of MTMR6, suggesting that Rab1B regulates the localization of MTMR6. The reduction of MTMR6 accelerated the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibited the formation of the tubular omegasome that is induced by overexpression of DFCP1 in autophagy. Our results indicate that the cellular localization of MTMR6 is regulated by Rab1B in the early secretory and autophagic pathways. We propose a new regulatory mechanism of myotubularin phosphatase by the small GTPase Rab1B.
authors.affiliation: Department of Molecular Biology and Medicine, The University of Tokyo, Tokyo 153-8904, Japan. mochizuki@lsbm.org
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Riuko
authors.initials: R
authors.lastname: Ohashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
mesh_terms: D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; C513490:MTMR6 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C061816:phosphatidylinositol-3-phosphatase; C529587:Rab1B protein, human; D020761:rab1 GTP-Binding Proteins