title: Receptor mediated endocytosis 8 is a novel PI(3)P binding protein regulated by myotubularin-related 2.
abstract: Myotubularin related protein 2 (MTMR2) is a member of the myotubularin family of phosphoinositide lipid phosphatases. Although MTMR2 dephosphorylates the phosphoinositides PI(3)P and PI(3,5)P2, the phosphoinositide binding proteins that are regulated by MTMR2 are poorly characterized. In this study, phosphoinositide affinity chromatography coupled to mass spectrometry identified receptor mediated endocytosis 8 (RME-8) as a novel PI(3)P binding protein. RME-8 co-localized with the PI(3)P marker DsRed-FYVE, while the N-terminal region of RME-8 is required for PI(3)P and PI(3,5)P(2) binding in vitro. Depletion of PI(3)P by MTMR2 S58A or wortmannin treatment attenuated RME-8 endosomal localization and co-localization with EGFR on early endosomes. Our results suggest a model in which the localization of RME-8 to endosomal compartments is spatially mediated by PI(3)P binding and temporally regulated by MTMR2 activity.
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.
authors.forename: Besa
authors.initials: B
authors.lastname: Xhabija
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Taylor
authors.forename: Akemi
authors.initials: A
authors.lastname: Fujibayashi
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: Panayiotis O
authors.initials: PO
authors.lastname: Vacratsis
mesh_terms: D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D018832:Molecular Chaperones / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000502:physiology*; D051381:Rats
chemical_list: D002352:Carrier Proteins; C507526:DNAJC13 protein, rat; D018832:Molecular Chaperones; D010716:Phosphatidylinositols; C520716:MTMR2 protein, rat; D054558:Protein Tyrosine Phosphatases, Non-Receptor