title: Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts.
abstract: Rab7 has been shown to regulate the late steps of the endocytic pathway. In bone-resorbing osteoclasts, it is involved in formation of the ruffled border, which is a late endosomal-like compartment in the plasma membrane. Here we report a new Rab7-interacting protein, Rac1, another small GTPase protein that binds to the GTP-form of Rab7 as found with a two-hybrid system. We demonstrate further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts. In other cell types, such as fibroblast-like cells, partial colocalization is perinuclear. Because Rac1 is known to control the actin cytoskeleton through its effectors, the Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments enabling endosomal vesicles to switch tracks and may thus also regulate ruffled border formation in osteoclasts.
authors.affiliation: Department of Anatomy, Institute of Biomedicine, University of Turku, Finland.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Kalman G
authors.initials: KG
authors.lastname: Büki
authors.forename: Otto
authors.initials: O
authors.lastname: Ettala
authors.forename: Jukka P
authors.initials: JP
authors.lastname: Vääräniemi
authors.forename: H Kalervo
authors.initials: HK
authors.lastname: Väänänen
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D020558:GTP Phosphohydrolases / Q000737:chemistry; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D007425:Intracellular Membranes / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000737:chemistry*; D000090802:rab7 GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein / Q000737:chemistry*
chemical_list: D000199:Actins; D018076:DNA, Complementary; D000090802:rab7 GTP-Binding Proteins; C000716466:rab7 GTP-binding proteins, rat; D006639:Histidine; D005982:Glutathione Transferase; D020558:GTP Phosphohydrolases; D020691:rab GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein