title: The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex.
abstract: This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization. Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in punctuate structures. Coexpression of Rab5a (WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling.
authors.affiliation: Departments of Obstetrics and Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0617, USA.
authors.forename: Thippeswamy
authors.initials: T
authors.lastname: Gulappa
authors.forename: Christine L
authors.initials: CL
authors.lastname: Clouser
authors.forename: K M J
authors.initials: KM
authors.lastname: Menon
mesh_terms: D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000032:analysis / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D011974:Receptors, LH / Q000032:analysis / Q000378:metabolism*; D014162:Transfection; D020696:rab5 GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D020696:rab5 GTP-Binding Proteins