title: Retinal degeneration modulates intracellular localization of CDC42 in photoreceptors.
abstract: OBJECTIVE
  Rho GTPases such as RAS-related C3 botulinum substrate 1 (RAC1) and cell division cycle 42 homolog (S. cerevisiae; CDC42) have been linked to cellular processes including movement, development, and apoptosis. Recently, RAC1 has been shown to be a pro-apoptotic factor in the retina during light-induced photoreceptor degeneration. Here, we analyzed the role of CDC42 in the degenerating retina.
  
  
  METHODS
  Photoreceptor degeneration was studied in a mouse model for autosomal dominant retinitis pigmentosa (VPP) with or without a rod-specific knockdown of Cdc42, as well as in wild-type and Cdc42 knockdown mice after light exposure. Gene and protein expression were analyzed by real-time PCR, western blotting, and immunofluorescence. Retinal morphology and function were assessed by light microscopy and electroretinography, respectively.
  
  
  RESULTS
  CDC42 accumulated in the perinuclear region of terminal deoxynucleotidyl transferase dUTP nick end labeling-negative photoreceptors during retinal degeneration induced by excessive light exposure and in the rd1, rd10, and VPP mouse models of retinitis pigmentosa. The knockdown of Cdc42 did not affect retinal morphology or function in the adult mice and did not influence photoreceptor apoptosis or molecular signaling during induced and inherited retinal degeneration.
  
  
  CONCLUSIONS
  Retinal degeneration induces the accumulation of CDC42 in the perinuclear region of photoreceptors. In contrast to RAC1, however, lack of CDC42 does not affect the progression of degeneration. CDC42 is also dispensable for normal morphology and function of adult rod photoreceptor cells. RECEIVED: May 25, 2011 ACCEPTED: November 10, 2011.
authors: Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Switzerland. severin.heynen@usz.ch
authors: S R
authors: SR
authors: Heynen
authors: N
authors: N
authors: Tanimoto
authors: S
authors: S
authors: Joly
authors: M W
authors: MW
authors: Seeliger
authors: M
authors: M
authors: Samardzija
authors: C
authors: C
authors: Grimm
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics; D015870:Gene Expression / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism
chemical_list: C115491:Arhgap31 protein, mouse; D020690:GTPase-Activating Proteins; D012243:Rhodopsin; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse