title: Human RME-8 is involved in membrane trafficking through early endosomes.
abstract: RME-8 is a DnaJ-domain-containing protein that was first identified in Caenorhabditis elegans as being required for uptake of yolk proteins. RME-8 has also been identified in other species, including flies and mammals, and the phenotypes of their RME-8 mutants suggest the importance of this protein in endocytosis. In the present study, we cloned human RME-8 (hRME-8) and characterized its biochemical properties and functions in endocytic pathways. hRME-8 was found to be a peripheral protein that was tightly associated with the membrane via its N-terminal region. It partially colocalized with several early endosomal markers, but not with late endosomal markers, consistent with observations by immunoelectron microscopy. When cells were transfected with a panel of dominant-active Rab proteins, hRME-8 was confined to large vacuoles induced by expression of Rab5aQ79L, but not by Rab7Q67L. Expression of C-terminally-truncated hRME-8 mutants led to the formation of large puncta and vacuoles, and compromised endocytic pathways through early endosomes, i.e., recycling of transferrin and degradation of epidermal growth factor. Taken together, these results indicate that hRME is primarily involved in membrane trafficking through early endosomes, but not through degradative organelles, such as multivesicular bodies and late endosomes.
authors.affiliation: Division of Protein Chemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Fujibayashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taguchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Misaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohtani
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Koji
authors.initials: K
authors.lastname: Takio
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
authors.forename: Megumi
authors.initials: M
authors.lastname: Yamakami
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D003001:Cloning, Molecular; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013194:Staining and Labeling; D014617:Vacuoles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C507525:DNAJC13 protein, human; D018832:Molecular Chaperones; D020691:rab GTP-Binding Proteins