title: Hook2 contributes to aggresome formation.
abstract: BACKGROUND
  Aggresomes are pericentrosomal accumulations of misfolded proteins, chaperones and proteasomes. Their positioning near the centrosome, like that of other organelles, requires active, microtubule-dependent transport. Linker proteins that can associate with the motor protein dynein, organelles, and microtubules are thought to contribute to the active maintenance of the juxtanuclear localization of many membrane bound organelles and aggresomes. Hook proteins have been proposed to serve as adaptors for the association of cargos with dynein for transport on microtubules. Hook2 was shown to localize to the centrosome, bind centriolin, and contribute to centrosomal function.
  
  
  RESULTS
  Here we show that overexpression of hook2 promotes the accumulation of the cystic fibrosis transmembrane regulator in aggresomes without altering its biochemical properties or its steady state level. A dominant negatively acting form of hook2 that lacks the centriolin binding C-terminal inhibits aggresome formation.
  
  
  CONCLUSIONS
  We propose that hook2 contributes to the establishment and maintenance of the pericentrosomal localization of aggresomes by promoting the microtubule-based delivery of protein aggregates to pericentriolar aggresomes.
authors.affiliation: Center for Basic Neuroscience, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9111, USA. gspb@prodigy.net <gspb@prodigy.net>
authors.forename: Györgyi
authors.initials: G
authors.lastname: Szebenyi
authors.forename: W Christian
authors.initials: WC
authors.lastname: Wigley
authors.forename: Branden
authors.initials: B
authors.lastname: Hall
authors.forename: Aaron
authors.initials: A
authors.lastname: Didier
authors.forename: Michelle
authors.initials: M
authors.lastname: Yu
authors.forename: Philip
authors.initials: P
authors.lastname: Thomas
authors.forename: Helmut
authors.initials: H
authors.lastname: Krämer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D021381:Protein Transport; D014018:Tissue Distribution; D014162:Transfection; D014709:Vero Cells
chemical_list: C521349:Hook2 protein, human; D008869:Microtubule-Associated Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator