title: Intracellular membrane trafficking pathways in bone-resorbing osteoclasts revealed by cloning and subcellular localization studies of small GTP-binding rab proteins.
abstract: A variety of intracellular membrane trafficking pathways are involved in establishing the polarization of resorbing osteoclasts and regulating bone resorption activities. Small GTP-binding proteins of rab family have been implicated as key regulators of membrane trafficking in mammalian cells. Here we used a RT-PCR-based cloning method and confocal laser scanning microscopy to explore the expression array and subcellular localization of rab proteins in osteoclasts. Rab1B, rab4B, rab5C, rab7, rab9, rab11B, and rab35 were identified from rat osteoclasts in this study. Rab5C may be associated with early endosomes, while rab11B is localized at perinuclear recycling compartments and may function in the ruffled border membrane turnover and osteoclast motility. Interestingly, late endosomal rabs, rab7, and rab9, were found to localize at the ruffled border membrane indicating a late endosomal nature of this specialized plasma membrane domain in resorbing osteoclasts. This also suggests that late endocytotic pathways may play an important role in the secretion of lysosomal enzymes, such as cathepsin K, during bone resorption.
authors.affiliation: Department of Anatomy, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. hzhao@pathology.wustl.edu
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhao
authors.forename: Otto
authors.initials: O
authors.lastname: Ettala
authors.forename: H Kalervo
authors.initials: HK
authors.lastname: Väänänen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D001862:Bone Resorption; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D020691:rab GTP-Binding Proteins