Potential Cellular Functions of N-Ethylmaleimide Sensitive Factor in the Photoreceptor
N-ethylmaleimide sensitive factor (NSF) is an ATPase associated with a variety of cellular activities in the AAA protein family and is required for intracellular membrane fusion. We reported a novel synaptic protein–protein interaction between visual Arrestin 1 (Arr1) and NSF that is enhanced in a dark environment when photoreceptors are depolarized and the rate of exocytosis is elevated. In the photoreceptor synapse, NSF functions to sustain a tonic rate of exocytosis, in addition to the compensatory endocytosis to retrieve and to recycle vesicle membrane and synaptic proteins. In addition to the Arr1 and NSF interaction, NSF was shown to interact with the retinitis pigmentosa protein 2 (RP2) in the retina and may play an important role in membrane protein trafficking in photoreceptors. These studies demonstrate diverse roles of NSF in the photoreceptor synapse and in membrane protein trafficking and provide key insights into the potential molecular mechanisms of inherited retinal diseases, such as Oguchi disease and retinitis pigmentosa.
KeywordsArrestin 1 N-ethylmaleimide sensitive factor Retinitis pigmentosa protein 2 Phototransduction Oguchi disease NSF attachment proteins receptor Retinitis pigmentosa Synapses ATPase Protein trafficking
We thank members of the Mary D. Allen Laboratory for scientific discussions, Bruce M. Brown for his technical expertise, Lawrence Rife for ERG analysis, Ernesto Barron for preparation of figures, and Jeannie Chen for the Arr1 −/− mice. CMC is the Mary D. Allen Chair in Vision Research, DEI, and a Research to Prevent Blindness (RPB) Senior Scientific Investigator. This work was supported, in part, by NIH Grant EY015851 (CMC), EY03040 (DEI), RPB (DEI & CMC), Dorie Miller, Tony Gray Foundation, Mary D. Allen Foundation (Dr. Richard Newton Lolley Memorial Scholarship [SPH]), and a RD2010 Travel Award (SPH).
- Huang SP (2010) Exploring Alternative Roles of Visual Arrestin 1 in Photoreceptor Synaptic Regulation and Deciphering the Molecular Pathway of Retinal Degeneration Using Mouse Knockout Technology. Ph.D. dissertation. University of Southern CaliforniaGoogle Scholar