Abstract
NCS1 (neuronal calcium sensor-1) is a Ca2+-myristoyl switch protein of the NCS protein family involved in synaptic plasticity and neurotransmission via Ca2+-dependent regulation of dopamine D2 receptor and associated Gprotein coupled receptor kinase (GRK)-2. Overexpression of NCS1 in synaptic terminals results in accumulation of membrane-bound protein and its redundant regulatory activity associated with neurological disorders. Here, we have demonstrated that bovine photoreceptors contain NCS1 that is capable of a partially irreversible interaction with isolated photoreceptor membranes and implicated in Ca2+-dependent binding and regulation of GRK1 in vitro. Using NCS1- recoverin C-terminal chimeric construct (NR), it was found that the Ca2+-myristoyl switch of NCS1 is affected by its Cterminal segment downstream the fourth EF-loop of the protein, which is variable within the NCS family. NR retains structural stability and sensitivity to Ca2+, but interacts with photoreceptor membranes with lower affinity in a Ca2+- dependent fully reversible manner and displays altered GRK1 modulation. These data combined with fluorescent probing of surface hydrophobicity of NCS1, NR and recoverin suggest that the C-terminal segment of NCS1 regulates reuptake of myristoyl group under Ca2+-free conditions and participates in organization of the target-binding pocket of the protein. We point out a putative role of NCS1 in photoreceptors as a modulator of GRK activity and propose targeting of the Cterminal segment of NCS1 as an appropriate way for selective suppression of excessive membrane accumulation and aberrant activity of the protein in neurons associated with central nervous system dysfunctions.
Keywords: C-terminal segment, Ca2+-myristoyl switch, G-protein coupled receptor kinase, membrane interaction, neurological disorders, neuronal calcium sensor-1, neuronal calcium sensor protein family, retinal neurons.
CNS & Neurological Disorders - Drug Targets
Title:Ca2+-Myristoyl Switch in Neuronal Calcium Sensor-1: A Role of C-Terminal Segment
Volume: 14 Issue: 4
Author(s): Viktoriia E. Baksheeva, Aliya A. Nazipova, Dmitry V. Zinchenko, Marina V. Serebryakova, Ivan I. Senin, Sergei E. Permyakov, Pavel P. Philippov, Yi Li, Andrey A. Zamyatnin, Evgeni Y. Zernii and Gjumrakch Aliev
Affiliation:
Keywords: C-terminal segment, Ca2+-myristoyl switch, G-protein coupled receptor kinase, membrane interaction, neurological disorders, neuronal calcium sensor-1, neuronal calcium sensor protein family, retinal neurons.
Abstract: NCS1 (neuronal calcium sensor-1) is a Ca2+-myristoyl switch protein of the NCS protein family involved in synaptic plasticity and neurotransmission via Ca2+-dependent regulation of dopamine D2 receptor and associated Gprotein coupled receptor kinase (GRK)-2. Overexpression of NCS1 in synaptic terminals results in accumulation of membrane-bound protein and its redundant regulatory activity associated with neurological disorders. Here, we have demonstrated that bovine photoreceptors contain NCS1 that is capable of a partially irreversible interaction with isolated photoreceptor membranes and implicated in Ca2+-dependent binding and regulation of GRK1 in vitro. Using NCS1- recoverin C-terminal chimeric construct (NR), it was found that the Ca2+-myristoyl switch of NCS1 is affected by its Cterminal segment downstream the fourth EF-loop of the protein, which is variable within the NCS family. NR retains structural stability and sensitivity to Ca2+, but interacts with photoreceptor membranes with lower affinity in a Ca2+- dependent fully reversible manner and displays altered GRK1 modulation. These data combined with fluorescent probing of surface hydrophobicity of NCS1, NR and recoverin suggest that the C-terminal segment of NCS1 regulates reuptake of myristoyl group under Ca2+-free conditions and participates in organization of the target-binding pocket of the protein. We point out a putative role of NCS1 in photoreceptors as a modulator of GRK activity and propose targeting of the Cterminal segment of NCS1 as an appropriate way for selective suppression of excessive membrane accumulation and aberrant activity of the protein in neurons associated with central nervous system dysfunctions.
Export Options
About this article
Cite this article as:
Baksheeva E. Viktoriia, Nazipova A. Aliya, Zinchenko V. Dmitry, Serebryakova V. Marina, Senin I. Ivan, Permyakov E. Sergei, Philippov P. Pavel, Li Yi, Zamyatnin A. Andrey, Zernii Y. Evgeni and Aliev Gjumrakch, Ca2+-Myristoyl Switch in Neuronal Calcium Sensor-1: A Role of C-Terminal Segment, CNS & Neurological Disorders - Drug Targets 2015; 14 (4) . https://dx.doi.org/10.2174/1871527314666150225143403
DOI https://dx.doi.org/10.2174/1871527314666150225143403 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Risk Communication of Vaccines: Challenges in the Post-Trust Environment
Current Drug Safety Integral Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells
Current Drug Targets Inhibition of Transcription Factors by Plant-Derived Compounds and their Implications in Inflammation and Cancer
Current Pharmaceutical Design Targeting Sphingosine-1-Phosphate Receptors in Cancer
Anti-Cancer Agents in Medicinal Chemistry Physicochemical Parameters of Non-Viral Vectors that Govern Transfection Efficiency
Current Gene Therapy Role of Endogenous Granulocyte-Macrophage Colony Stimulating Factor Following Stroke and Relationship to Neurological Outcome
Current Neurovascular Research Atypical Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children: A Systematic Review
Current Pediatric Reviews Removal of the Tag from His-tagged ILYd4, a Human CD59 Inhibitor, Significantly Improves its Physical Properties and its Activity
Current Pharmaceutical Design Q-TOF LC/MS-based Untargeted Metabolomics Approach to Evaluate the Effect of Folate-Conjugated Cyclodextrins on Triple-Negative Breast Cancer Cells
Current Pharmaceutical Analysis Pharmacogenetics and the Pharmaceutical Industry
Current Pharmaceutical Design Intranasal Drug Delivery for Brain Targeting
Current Drug Delivery Meet Our Assoicate Editor
Current Radiopharmaceuticals An Uncommon Case of Symptomatic Multiple Meningiomas with Bilateral Compressive Optic Neuropathy Rapidly Induced under Cyprotero ne Acetate Treatment
Current Drug Safety Baicalin Suppresses Migration, Invasion and Metastasis of Breast Cancer via p38MAPK Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Metronidazole Induced DNA Damage in Somatic Cells of Drosophila melanogaster
Current Drug Safety The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets Recent Progress in the Synthesis of Flavonoids: From Monomers to Supra-Complex Molecules
Current Organic Chemistry MicroRNA and Exosome in Retinal-related Diseases: Their Roles in the Pathogenesis and Diagnosis
Combinatorial Chemistry & High Throughput Screening Zinc and its Specific Transporters as Potential Targets in Airway Disease
Current Drug Targets Microglia NLRP3 Inflammasomes Activation Involving Diabetic Neuroinflammation in Diabetic Mice and BV2 Cells
Current Pharmaceutical Design