Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guanylate cyclase activating protein 2 (GCAP2) is a recoverin-like Ca2+-sensor protein known to modulate guanylate cyclase activity in photoreceptor outer segments. GCAP2 is also present in photoreceptor ribbon synapses where its function is unknown. Synaptic ribbons are active zone-associated presynaptic structures in the tonically active photoreceptor ribbon synapses and contain RIBEYE as a unique and major protein component. In the present study, we demonstrate by various independent approaches that GCAP2 specifically interacts with RIBEYE in photoreceptor synapses. We show that the flexible hinge 2 linker region of RIBEYE(B) domain that connects the nicotinamide adenine dinucleotide (NADH)-binding subdomain with the substrate-binding subdomain (SBD) binds to the C terminus of GCAP2. We demonstrate that the RIBEYE-GCAP2 interaction is induced by the binding of NADH to RIBEYE. RIBEYE-GCAP2 interaction is modulated by the SBD. GCAP2 is strongly expressed in synaptic terminals of light-adapted photoreceptors where GCAP2 is found close to synaptic ribbons as judged by confocal microscopy and proximity ligation assays. Virus-mediated overexpression of GCAP2 in photoreceptor synaptic terminals leads to a reduction in the number of synaptic ribbons. Therefore, GCAP2 is a prime candidate for mediating Ca2+-dependent dynamic changes of synaptic ribbons in photoreceptor synapses.
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PMID:Nicotinamide adenine dinucleotide-dependent binding of the neuronal Ca2+ sensor protein GCAP2 to photoreceptor synaptic ribbons. 2046 19

Changes in intracellular calcium ions [Ca(2+)] play important roles in photoreceptor signaling. Consequently, intracellular [Ca(2+)] levels need to be tightly controlled. In the light-sensitive outer segments (OS) of photoreceptors, Ca(2+) regulates the activity of retinal guanylate cyclases thus playing a central role in phototransduction and light-adaptation by restoring light-induced decreases in cGMP. In the synaptic terminals, changes of intracellular Ca(2+) trigger various aspects of neurotransmission. Photoreceptors employ tonically active ribbon synapses that encode light-induced, graded changes of membrane potential into modulation of continuous synaptic vesicle exocytosis. The active zones of ribbon synapses contain large electron-dense structures, synaptic ribbons, that are associated with large numbers of synaptic vesicles. Synaptic coding at ribbon synapses differs from synaptic coding at conventional (phasic) synapses. Recent studies revealed new insights how synaptic ribbons are involved in this process. This review focuses on the regulation of [Ca(2+)] in presynaptic photoreceptor terminals and on the function of a particular Ca(2+)-regulated protein, the neuronal calcium sensor protein GCAP2 (guanylate cyclase-activating protein-2) in the photoreceptor ribbon synapse. GCAP2, an EF-hand-containing protein plays multiple roles in the OS and in the photoreceptor synapse. In the OS, GCAP2 works as a Ca(2+)-sensor within a Ca(2+)-regulated feedback loop that adjusts cGMP levels. In the photoreceptor synapse, GCAP2 binds to RIBEYE, a component of synaptic ribbons, and mediates Ca(2+)-dependent plasticity at that site. Possible mechanisms are discussed.
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PMID:Presynaptic [Ca(2+)] and GCAPs: aspects on the structure and function of photoreceptor ribbon synapses. 2456 2