Photoreceptor calcium sensor proteins in detergent-resistant membrane rafts are regulated via binding to caveolin-1. (July 2018)

• Record Type: Journal Article
• Authors: Vladimirov, Vasiliy I.; Zernii, Evgeni Yu; Baksheeva, Viktoriia E.; Wimberg, Hanna; Kazakov, Alexey S.; Tikhomirova, Natalya K.; Nemashkalova, Ekaterina L.; Mitkevich, Vladimir A.; Zamyatnin, Andrey A.; Lipkin, Valery M.; Philippov, Pavel P.; Permyakov, Sergei E.; Senin, Ivan I.; Koch, Karl-W.; Zinchenko, Dmitry V.
• Is Part Of: Cell calcium. Volume 73(2018)
• Page Start: 55
• Page End: 69
• Publication Date: 2018-07
• Subjects: Cav1-101 N-terminal fragment of bovine caveolin-1 -- Cav81–101 peptide corresponding to scaffold domain of bovine caveolin-1 -- CNS central nervous system -- CAC critical aggregation concentration -- DRM detergent-resistant membrane -- EF1–EF4 EF-hand Ca2+-binding sites -- GCAP guanylate cyclase-activating protein -- GPCR G-protein coupled receptor -- H1–H10 α-helixes of neuronal calcium sensor proteins examined in the study -- HPLC high-performance liquid chromatography -- ITC isothermal titration calorimetry -- MA myrisitic acid -- NCS neuronal calcium sensor -- PDE6 phosphodiesterase 6 -- RGS9 regulator of G-protein signaling 9 (RGS9) -- RIS rod inner segment -- RK rhodopsin kinase (GRK1) -- ROS rod outer segment -- ROS-GC rod outer segment guanylate cyclase -- SD standard deviation -- SPR surface plasmon resonance, WT, wild type protein; Rod outer segment (ROS) -- Detergent-resistant membrane (DRM) rafts -- Caveolin-1 -- Recoverin -- Neuronal calcium sensor-1 (NCS1) -- Guanylate cyclase-activating protein 1 (GCAP1) -- Guanylate cyclase-activating protein 2 (GCAP2); Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2018.04.003
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: NCS proteins contain conservative caveolin-1 binding site in their C-terminal domain. Recoverin, NCS1, GCAP1, and GCAP2 co-localize with caveolin-1 in ROS membrane rafts. NCS proteins bind to scaffolding domain of caveolin-1 at low calcium. Caveolin-1 enhances activity of Ca 2+ -free GCAP2 towards ROS guanylate cyclase-1. Caveolin-1 increases Ca 2+ affinity of recoverin by affecting its Ca2+-myristoyl switch. Abstract: Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca 2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners. All four NCS proteins co-fractionate with caveolin-1 in DRMs, isolated from illuminated bovine rod outer segments. According to pull-down assay, surface plasmon resonance spectroscopy and isothermal titration calorimetry data, they are capable of high-affinity binding to either N-terminal fragment of caveolin-1 (1–101), or its short scaffolding domain (81–101) via a novel structural site. In recoverin this site is localized in C-terminal domain in proximity to the third EF-hand motif and composed of aromatic amino acids conserved among NCS proteins. Remarkably, the binding of NCS proteins to caveolin-1 occurs only in the absence of calcium, which is in agreement with higher accessibility of the caveolin-1 binding site in their Ca 2+ -free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca 2+ -saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca 2+ -free conformation. In addition, the interaction with caveolin-1 decreases cooperativity and augments affinity of Ca2 + binding to recoverin apparently by facilitating exposure of its myristoyl group. We suggest that at low calcium NCS proteins are compartmentalized in photoreceptor rafts via binding to caveolin-1, which may enhance their activity or ensure their faster responses on Ca 2+ -signals thereby maintaining efficient phototransduction recovery and light adaptation.