Knockdown of poc1b causes abnormal photoreceptor sensory cilium and vision impairment in zebrafish

Biochem Biophys Res Commun. 2015 Oct 2;465(4):651-7. doi: 10.1016/j.bbrc.2015.06.083. Epub 2015 Jul 15.

Abstract

Proteomic analysis of the mouse photoreceptor sensory cilium identified a set of cilia proteins, including Poc1 centriolar protein b (Poc1b). Previous functional studies in human cells and zebrafish embryos implicated that Poc1b plays important roles in centriole duplication and length control, as well as ciliogenesis. To study the function of Poc1b in photoreceptor sensory cilia and other primary cilia, we expressed a tagged recombinant Poc1b protein in cultured renal epithelial cells and rat retina. Poc1b was localized to the centrioles and spindle bundles during cell cycle progression, and to the basal body of photoreceptor sensory cilia. A morpholino knockdown and complementation assay of poc1b in zebrafish showed that loss of poc1b led to a range of morphological anomalies of cilia commonly associated with human ciliopathies. In the retina, the development of retinal laminae was significantly delayed and the length of photoreceptor outer segments was shortened. Visual behavior studies revealed impaired visual function in the poc1b morphants. In addition, ciliopathy-associated developmental defects, such as small eyes, curved body axis, heart defects, and shortened cilia in Kupffer's vesicle, were observed as well. These data suggest that poc1b is required for normal development and ciliogenesis of retinal photoreceptor sensory cilia and other cilia. Furthermore, this conclusion is supported by recent findings that mutations in POC1B gene have been identified in patients with inherited retinal dystrophy and syndromic retinal ciliopathy.

Keywords: Basal body; Ciliopathy; Inherited retinal degenerations (IRDs); Photoreceptor sensory cilia (PSC); Zebrafish; poc1b.

Publication types

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

MeSH terms

  • Animals
  • CHO Cells
  • Cell Cycle Proteins / genetics
  • Centrioles / physiology
  • Cilia / physiology
  • Cricetulus
  • Gene Knockdown Techniques
  • Genetic Complementation Test
  • Heart Defects, Congenital / genetics
  • Humans
  • Mice
  • Mutation
  • Photoreceptor Connecting Cilium / physiology*
  • Proteomics
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retinal Dystrophies / genetics
  • Vision Disorders / genetics
  • Vision Disorders / physiopathology
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / physiology*
  • Zebrafish Proteins / antagonists & inhibitors*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • POC1B protein, human
  • Recombinant Proteins
  • Zebrafish Proteins