Neuronal Calcium Sensor 1: a Zinc/Redox-Dependent Protein of Nervous System Signaling Pathways

Abstract

Intracellular calcium signals play a key role in the regulation of nervous system structure and function. 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. In recent decades, a family of highly specialized neuronal proteins that can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors has been described. The most abundant member of this family is neuronal calcium sensor-1 (NCS-1), which is intensively expressed in CNS neurons and controls such vital processes as neuronal growth and survival, reception, neurotransmission and synaptic plasticity. In addition to calcium ions, NCS-1 may bind intracellular ‘mobile’ zinc, increased concentration of which is a characteristic feature of cells under oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. The combined effect of mobile zinc and the increased redox potential of the medium can thus induce the aberrant NCS-1 activity involving signals for survival of neuronal cells or induction of their apoptosis and, as a consequence, the development of neurodegenerative processes. The review details the localization, regulation of expression, structure and molecular properties of NCS-1, as well as current data on its signaling activity in health and disease, including zinc-dependent redox-regulation cascades.