title: Hook2 is involved in the morphogenesis of the primary cilium.
abstract: Primary cilia originate from the centrosome and play essential roles in several cellular, developmental, and pathological processes, but the underlying mechanisms of ciliogenesis are not fully understood. Given the involvement of the adaptor protein Hook2 in centrosomal homeostasis and protein transport to pericentrosomal aggresomes, we explored its role in ciliogenesis. We found that in human retinal epithelial cells, Hook2 localizes at the Golgi apparatus and centrosome/basal body, a strategic partitioning for ciliogenesis. Of importance, Hook2 depletion disrupts ciliogenesis at a stage before the formation of the ciliary vesicle at the distal tip of the mother centriole. Using two hybrid and immunoprecipitation assays and a small interfering RNA strategy, we found that Hook2 interacts with and stabilizes pericentriolar material protein 1 (PCM1), which was reported to be essential for the recruitment of Rab8a, a GTPase that is believed to be crucial for membrane transport to the primary cilium. Of interest, GFP::Rab8a coimmunoprecipitates with endogenous Hook2 and PCM1. Finally, GFP::Rab8a can overcome Hook2 depletion, demonstrating a functional interaction between Hook2 and these two important regulators of ciliogenesis. The data indicate that Hook2 interacts with PCM1 in a complex that also contains Rab8a and regulates a limiting step required for further initiation of ciliogenesis after centriole maturation.
authors: CNRS UMR 6216, IBDML, Université de la Méditerranée, 13288 Marseille Cedex 09, France.
authors: Carole L
authors: CL
authors: Baron Gaillard
authors: Emilie
authors: E
authors: Pallesi-Pocachard
authors: Dominique
authors: D
authors: Massey-Harroche
authors: Fabrice
authors: F
authors: Richard
authors: Jean-Pierre
authors: JP
authors: Arsanto
authors: Jean-Paul
authors: JP
authors: Chauvin
authors: Patrick
authors: P
authors: Lecine
authors: Helmut
authors: H
authors: Krämer
authors: Jean-Paul
authors: JP
authors: Borg
authors: André
authors: A
authors: Le Bivic
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; C521349:Hook2 protein, human; C546999:Hook2 protein, mouse; D008869:Microtubule-Associated Proteins; C086074:PCM1 protein, human; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins