title: Hook2 localizes to the centrosome, binds directly to centriolin/CEP110 and contributes to centrosomal function.
abstract: Centrosomes serve as microtubule-organizing centers. However, centrosome function depends on microtubule organization and protein transport because the formation, positioning and maintenance of centrosomes require microtubule-dependent retrograde transport. Linker proteins that associate with the motor protein dynein, organelles and microtubules facilitate loading of cargos for retrograde transport and thus contribute to the composition and placement of the centrosome and other juxtanuclear protein complexes. Members of the hook family of proteins may function as adaptors to link various organelle cargos to dynein for transport and have also been implicated directly in centrosome positioning. Here, we show that mammalian hook2, a previously uncharacterized member of the hook family, localizes to the centrosome through all phases of the cell cycle, the C-terminal domain of hook2 directly binds to centriolin/CEP110, the expression of the C-terminal domain of centriolin/CEP110 alters the distribution of endogenous hook2 and mislocalized wild-type or mutant hook2 proteins perturb endogenous centrosomal and pericentrosomal proteins in cultured mammalian cells. In addition, interference with hook2 function results in the loss of the radial organization of microtubules and a defect in regrowth of microtubules following their nocodazole-induced depolymerization. Thus, we propose that hook2 contributes to the establishment and maintenance of centrosomal structure and function.
authors.affiliation: Center for Basic Neuroscience, University of Texas, Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9111, USA.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Szebenyi
authors.forename: Branden
authors.initials: B
authors.lastname: Hall
authors.forename: Rosa
authors.initials: R
authors.lastname: Yu
authors.forename: Arig Ibrahim
authors.initials: AI
authors.lastname: Hashim
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014018:Tissue Distribution; D014709:Vero Cells
chemical_list: C467559:CCP110 protein, human; C474898:CNTRL protein, human; D018797:Cell Cycle Proteins; C521349:Hook2 protein, human; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins