TY - JOUR T1 - Nicotinamide Adenine Dinucleotide-Dependent Binding of the Neuronal Ca<sup>2+</sup> Sensor Protein GCAP2 to Photoreceptor Synaptic Ribbons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6559 LP - 6576 DO - 10.1523/JNEUROSCI.3701-09.2010 VL - 30 IS - 19 AU - Jagadeesh Kumar Venkatesan AU - Sivaraman Natarajan AU - Karin Schwarz AU - Sabine I. Mayer AU - Kannan Alpadi AU - Venkat Giri Magupalli AU - Ching-Hwa Sung AU - Frank Schmitz Y1 - 2010/05/12 UR - http://www.jneurosci.org/content/30/19/6559.abstract N2 - 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. ER -