title: Effects of low AIPL1 expression on phototransduction in rods.
abstract: OBJECTIVE
  To investigate the impact of aryl hydrocarbon receptor-interacting protein-like (AIPL)-1 on photoreception in rods.
  
  
  METHODS
  Photoresponses of mouse rods expressing lowered amounts of AIPL1 were studied by single-cell and electroretinogram (ERG) recordings. Phototransduction protein levels and enzymatic activities were determined in biochemical assays. Ca2+ dynamics were probed with a fluorescent dye. Comparisons were made to rods expressing mutant Y99C guanylate cyclase activating protein (GCAP)-1, to understand which effects arose from elevated dark levels of cGMP and Ca2+.
  
  
  RESULTS
  Except for PDE, transduction protein levels were normal in low-AIPL1 retinas, as were guanylate cyclase (GC), rhodopsin kinase (RK), and normalized phosphodiesterase (PDE) activities. Y99C and low-AIPL1 rods were more sensitive to flashes than normal, but flash responses of low-AIPL1 rods showed an abnormal delay, reduced rate of increase, and longer recovery not present in Y99C rod responses. In addition, low-AIPL1 rods but not Y99C rods failed to reach the normal light-induced minimum in Ca2+ concentration.
  
  
  CONCLUSIONS
  Reduced AIPL1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in Ca2+. Not all changes were attributable to decreased PDE or to elevated cGMP and Ca2+ in darkness. Therefore, AIPL1 directly or indirectly affects more than one component of phototransduction.
authors.affiliation: Howe Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston 02114, USA. cmakino@meei.harvard.edu
authors.forename: Clint L
authors.initials: CL
authors.lastname: Makino
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wen
authors.forename: Norman
authors.initials: N
authors.lastname: Michaud
authors.forename: Igor V
authors.initials: IV
authors.lastname: Peshenko
authors.forename: Basil
authors.initials: B
authors.lastname: Pawlyk
authors.forename: Richard S
authors.initials: RS
authors.lastname: Brush
authors.forename: Maria
authors.initials: M
authors.lastname: Soloviev
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Woodruff
authors.forename: Peter D
authors.initials: PD
authors.lastname: Calvert
authors.forename: Andrey B
authors.initials: AB
authors.lastname: Savchenko
authors.forename: Robert E
authors.initials: RE
authors.lastname: Anderson
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Fain
authors.forename: Tiansen
authors.initials: T
authors.lastname: Li
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sandberg
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Dizhoor
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002849:Chromatography, Gas; D006152:Cyclic GMP / Q000378:metabolism; D004596:Electroretinography; D005227:Fatty Acids / Q000378:metabolism; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D051604:Guanylate Cyclase-Activating Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010775:Photic Stimulation; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology* / Q000528:radiation effects; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C498604:Aipl1 protein, mouse; D002352:Carrier Proteins; D005227:Fatty Acids; D051604:Guanylate Cyclase-Activating Proteins; C496737:Guca1a protein, mouse; D051606:G-Protein-Coupled Receptor Kinase 1; D010727:Phosphoric Diester Hydrolases; D015293:Transducin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium