Hook2 is involved in the morphogenesis of the primary cilium

Mol Biol Cell. 2011 Dec;22(23):4549-62. doi: 10.1091/mbc.E11-05-0405. Epub 2011 Oct 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Centrosome / metabolism
  • Cilia / metabolism
  • Golgi Apparatus / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Sequence Data
  • RNA, Small Interfering
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism


  • Autoantigens
  • Cell Cycle Proteins
  • Hook2 protein, human
  • Hook2 protein, mouse
  • Microtubule-Associated Proteins
  • PCM1 protein, human
  • RNA, Small Interfering
  • Green Fluorescent Proteins
  • RAB8A protein, human
  • rab GTP-Binding Proteins