Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the G-protein-coupled receptor phototransduction cascade, visual Arrestin 1 (Arr1) binds to and deactivates phosphorylated light-activated opsins, a process that is critical for effective recovery and normal vision. In this report, we discovered a novel synaptic interaction between Arr1 and N-ethylmaleimide-sensitive factor (NSF) that is enhanced in a dark environment when mouse photoreceptors are depolarized and the rate of exocytosis is elevated. In the photoreceptor synapse, NSF functions to sustain a higher rate of exocytosis, in addition to the compensatory endocytosis to retrieve and to recycle vesicle membrane and synaptic proteins. Not only does Arr1 bind to the junction of NSF N-terminal and its first ATPase domains in an ATP-dependent manner in vitro, but Arr1 also enhances both NSF ATPase and NSF disassembly activities. In in vivo experiments in mouse retinas with the Arr1 gene knocked out, the expression levels of NSF and other synapse-enriched components, including vGLUT1 (vesicular glutamate transporter 1), EAAT5 (excitatory amino acid transporter 5), and VAMP2 (vesicle-associated membrane protein 2), are markedly reduced, which leads to a substantial decrease in the exocytosis rate with FM1-43. Thus, we propose that the Arr1 and NSF interaction is important for modulating normal synaptic function in mouse photoreceptors. This study demonstrates a vital alternative function for Arr1 in the photoreceptor synapse and provides key insights into the potential molecular mechanisms of inherited retinal diseases, such as Oguchi disease and Arr1-associated retinitis pigmentosa.
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PMID:Visual Arrestin 1 acts as a modulator for N-ethylmaleimide-sensitive factor in the photoreceptor synapse. 2063 Nov 67

Recent work has established potential new functional roles for NSF in the photoreceptor. First, the interaction of Arr1 and NSF is ATP-dependent, and the N-terminal domain of Arr1 interacts with the N and D1 junctional domains of NSF. The Arr1-NSF interactions are greater in the photoreceptor synaptic terminal in the dark. Furthermore, Arr1 enhances the NSF ATPase activity and increases the NSF disassembly activities, which are critical for NSF functions in sustaining a higher rate of exocytosis in the photoreceptor synapses and the compensatory endocytosis to retrieve vesicle membrane and vesicle proteins for vesicle recycling. These data demonstrate the Arr1 and NSF interaction are necessary for both maintenance and modulation of normal photoreceptor synaptic regulation. Second, NSF colocalizes and specifically binds to RP2, especially in the ciliary and synaptic region of the photoreceptor, and NSF-RP2 interaction may play an important role in membrane protein trafficking in the photoreceptor. Inherited retinal degeneration affects about 1 in 2,000-3,000 individuals in the world and is the leading cause of visual loss in young people and accounts for a large proportion of blindness in adult life. These studies accelerate our ability to gain insight into the diverse roles of the NSF in the photoreceptor cells and enable us to understand more precisely the molecular mechanisms underlying night blindness associated with clinically diagnosed Oguchi disease or other forms of retinitis pigmentosa.
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PMID:Potential cellular functions of N-ethylmaleimide sensitive factor in the photoreceptor. 2218 8