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Intracellular calcium signaling is involved in regulating the key functional mechanisms of the nervous system. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. A family of highly specialized neuronal proteins described in recent decades can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors. Neuronal calcium sensor-1 (NCS-1) is the most common member of the family, which is intensely expressed in central nervous system (CNS) cells; and controls several vital processes, such as neuronal growth and survival, reception, neurotransmission, and synaptic plasticity. In addition to calcium ions, NCS-1 can bind the so-called mobile, or signaling intracellular zinc, an increased concentration of which is a characteristic feature of cells in oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. A combined effect of mobile zinc and an increased redox potential of the medium can thus induce aberrant NCS-1 activity, including signals that promote survival of neuronal cells or induce their apoptosis and, consequently, the development of neurodegenerative processes. The review details the localization, expression regulation, structure, and molecular properties of NCS-1 and considers the current data on its signaling activity in health and disease, including zinc-dependent redox regulation cascades. [ABSTRACT FROM AUTHOR]

Neuronal calcium sensor-1 (NCS-1) is a member of neuronal calcium sensor family of proteins consisting of an amino terminal myristoylation domain and four conserved calcium (Ca) binding EF-hand domains. We performed site-directed mutational analysis of three key amino acid residues that are glycine in the conserved site for the N-terminal myristoylation, a conserved glutamic acid residue responsible for Ca binding in the third EF-hand (EF3), and an unusual non-conserved amino acid arginine at position 175 in the Neurospora crassa NCS-1. The N. crassa strains possessing the ncs- 1 mutant allele of these three amino acid residues showed impairment in functions ranging from growth, Ca stress tolerance, and ultraviolet survival. In addition, heterologous expression of the NCS-1 from Rattus norvegicus in N. crassa confirmed its interspecies functional conservation. Moreover, functions of glutamic acid at position 120, the first Ca binding residue among all the EF-hands of the R. norvegicus NCS-1 was found conserved. Thus, we identified three critical amino acid residues of N. crassa NCS-1, and demonstrated its functional conservation across species using the orthologue from R. norvegicus. [ABSTRACT FROM AUTHOR]

The article offers information on the interaction among three calcium-regulating gene products. Topics discussed include strains, growth, assay for calcium and ultraviolet (UV) sensitivity, circadian-regulated condition and effect of mutations in colony and carotenoid accumulation. Also present a graph that shows concentration of calcium chloride.

NCU04379 gene encodes a conserved Ca and/or calmodulin binding protein that possesses a consensus signal for N-terminal myristoylation and four EF-hands, characteristics of Neuronal Calcium Sensor-1proteins. The NCU04379.2 knockout mutant shows slow growth rate, increased sensitivity to calcium and ultraviolet (UV) irradiation, and a wild-type fragment carrying NCU04379 gene complements the mutant. Therefore, NCU04379 gene has a role in growth, calcium stress tolerance, and UV survival. Crosses homozygous for ΔNCU04379.2 mutant strains were fully fertile; however, we found evidence for involvement of Ca/calmodulin-dependent protein kinase encoding genes NCU02283 and NCU09123 in sexual development. [ABSTRACT FROM AUTHOR]

Neuronal calcium sensor-1 (NCS-1) interacts with many membranes and cytosolic proteins, both in a Ca-dependent and in a Ca-independent manner, and its physiological role is governed by its N-terminal myristoylation. To understand the role of myristoylation in altering Ca response and other basic biophysical properties, we have characterized the Ca filling pathways in both myristoylated (myr) and non-myristoylated (non-myr) forms of NCS-1. We have observed that Ca binds simultaneously to all three active EF-hands in non-myr NCS-1, whereas in the case of myr NCS-1, the process is sequential, where the second EF-hand is filled first, followed by the third and fourth EF-hands. In the case of myr NCS-1, the observed sequential Ca binding process becomes more prominent in the presence of Mg. Besides, the analysis of N-relaxation data reveals that non-myr NCS-1 is more dynamic than myr NCS-1. The overall molecular tumbling correlation time increases by approximately 20% upon myristoylation. Comparing the apo forms of non-myr NCS-1 and myr NCS-1, we found the possibility of existence of some substates, which are structurally closer to the holo form of the protein. There are more such substates in the case of non-myr NCS-1 than in the case of the myr NCS-1, suggesting that the former accesses larger volumes of conformational substates compared with the latter. Further, the study reveals that the possibility of Ca binding simultaneously to different parts of the protein is more favourable in non-myr NCS-1 than in myr NCS-1. [ABSTRACT FROM AUTHOR]

Calcium (Ca) is an important intracellular messenger underlying cell physiology. Ca channels are the main entry route for Ca into excitable cells, and regulate processes such as neurotransmitter release and neuronal outgrowth. Neuronal Calcium Sensor-1 (NCS-1) is a member of the Calmodulin superfamily of EF-hand Ca sensing proteins residing in the subfamily of NCS proteins. NCS-1 was originally discovered in Drosophila as an overexpression mutant ( Frequenin), having an increased frequency of Ca-evoked neurotransmission. NCS-1 is N-terminally myristoylated, can bind intracellular membranes, and has a Ca affinity of 0.3 μM. Over 10 years ago it was discovered that NCS-1 overexpression enhances Ca-evoked secretion in bovine adrenal chromaffin cells. The mechanism was unclear, but there was no apparent direct effect on the exocytotic machinery. It was revealed, again in chromaffin cells, that NCS-1 regulates voltage-gated Ca channels (Cavs) in G-Protein Coupled Receptor (GPCR) signaling pathways. This work in chromaffin cells highlighted NCS-1 as an important modulator of neurotransmission. NCS-1 has since been shown to regulate and/or directly interact with many proteins including Cavs (P/Q, N, and L), TRPC1/5 channels, GPCRs, IP3R, and PI4 kinase type IIIβ. NCS-1 also affects neuronal outgrowth having roles in learning and memory affecting both short- and long-term synaptic plasticity. It is not known if NCS-1 affects neurotransmission and synaptic plasticity via its effect on PIP2 levels, and/or via a direct interaction with Ca channels or their signaling complexes. This review gives a historical account of NCS-1 function, examining contributions from chromaffin cells, PC12 cells and other models, to describe how NCS-1's regulation of Ca channels allows it to exert its physiological effects. [ABSTRACT FROM AUTHOR]

Neuronal Calcium Sensor-1 (NCS-1) is a member of calcium sensor family. It is originally identified as frequenin. NCS-1 has been found to interact with membrane and cytosolic proteins and its physiological role is governed by N-terminal myristoylation. In this paper, we report the NMR assignments of both myristoylated and non-myristoylated NCS-1 in the presence of a membrane. [ABSTRACT FROM AUTHOR]

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