Structural, biochemical, and functional characterization of the calcium sensor neurocalcin delta in the inner retinal neurons and its linkage with the rod outer segment membrane guanylate cyclase transduction system.
This study documents the detailed biochemical, structural, and functional identity of a novel Ca(2+)-modulated membrane guanylate cyclase transduction system in the inner retinal neurons. The guanylate cyclase is the previously characterized ROS-GC1 from the photoreceptor outer segments (PROS), and its new modulator is neurocalcin delta. At the membrane, the myristoylated form of neurocalcin delta senses submicromolar increments in free Ca(2+), binds to its specific ROS-GC1 domain, and stimulates the cyclase. Neurocalcin delta is not present in PROS, indicating the absence of the pathway in the outer segments and the dissociation of its linkage with phototransduction. Thus, the pathway is linked specifically with the visual transduction machinery in the secondary neurons of the retina. With the inclusion of this pathway, the findings broaden the understanding of the existing mechanisms showing how ROS-GC1 is able to receive and transduce diverse Ca(2+) signals into the cell-specific generation of second-messenger cyclic GMP in the retinal neurons.
The Unit of Regulatory and Molecular Biology, Department of Cell Biology, SOM and NJMS, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084, USA.
Anuradha
A
Krishnan
Venkateswar
V
Venkataraman
Ewa
E
Fik-Rymarkiewicz
Teresa
T
Duda
Rameshwar K
RK
Sharma
D025042:Amacrine Cells / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000737:chemistry* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents / Q000737:chemistry; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000502:physiology; D019814:Myristic Acid / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D051596:Neurocalcin; D009474:Neurons / Q000737:chemistry* / Q000201:enzymology; D011485:Protein Binding; D044169:Receptors, Calcium-Sensing / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D012160:Retina / Q000737:chemistry* / Q000166:cytology / Q000201:enzymology; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000737:chemistry* / Q000201:enzymology; D020539:Sequence Analysis, Protein; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
D003432:Cross-Linking Reagents; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D044169:Receptors, Calcium-Sensing; D019814:Myristic Acid; D006162:Guanylate Cyclase; D002118:Calcium