Photoreceptor calcium sensor proteins in detergent-resistant membrane rafts are regulated via binding to caveolin-1 |
| |
| Affiliation: | 1. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia;2. Department of Cell Signaling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992 Russia;3. Department of Neurosciences, Biochemistry Group, University of Oldenburg, Oldenburg, 26111 Germany;4. Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia;5. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia;6. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow 119991, Russia;1. School of Biology, Georgia Institute of Technology, 310 Ferst Dr. NW, Atlanta, GA, USA;2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA;3. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;4. School of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA, USA;5. Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;1. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, 4029, Australia;2. Cognosco, Anexa FVC, Morrinsville, New Zealand;3. DairyNZ Ltd., Private Bag 3221, Hamilton, 3240, New Zealand;1. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991, Moscow, Russia;2. Anatomic Pathology Department, Sechenov First Moscow State Medical University, 119991, Moscow, Russia;3. Institute of Uronephrology and Human Reproductive Health, Sechenov First Moscow State Medical University, 119991, Moscow, Russia;4. Research Centre for Medical Genetics, 115522, Moscow, Russia;5. Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia;6. P.A. Hertzen Moscow Oncology Research Center, National Medical Research Center of Radiology, 125284, Moscow, Russia;7. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia;8. Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany;1. Department of Orthodontics, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China;2. Center for Craniofacial Stem Cell Research and Regeneration, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China;3. Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China;4. The 3rd Dental Center, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China;1. Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA;2. Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Sun Yat-sen University, 55 West Lingyuan Rd, Yuexiu District, Guangzhou 510055, China;3. Department of Pediatric Dentistry, School of Stomatology, China Medical University, 117 South Nanjing Street, Heping District, Shenyang 110002, China |
| |
| 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 Ca2+-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 Ca2+-free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca2+-saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca2+-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 Ca2+-signals thereby maintaining efficient phototransduction recovery and light adaptation. |
| |
| Keywords: | 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) |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
