Between promiscuity and specificity: novel roles of EF‐hand calcium sensors in neuronal Ca²⁺ signalling

Abstract

In recent years, substantial progress has been made towards an understanding of the physiological function of EF-hand calcium sensor proteins of the Calmodulin (CaM) superfamily in neurons. This deeper appreciation is based on the identification of novel target interactions, structural studies and the discovery of novel signalling mechanisms in protein trafficking and synaptic plasticity, in which CaM-like sensor proteins appear to play a role. However, not all interactions are of plausible physiological relevance and in many cases it is not yet clear how the CaM signaling network relates to the proposed function of other EF-hand sensors. In this review, we will summarize these findings and address some of the open questions on the functional role of EF-hand calcium binding proteins in neurons.

Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

“…In the spinal cord, the NECAB1/2 transcripts were up-regulated, with the time course of the former preceding that of the latter. -triggered neurotransmitter release and gene expression in neurons, and they may be important in the neuropathic pain process (7,13). DREAM (57) is a clearly defined EF-hand Ca 2+ sensor involved in modulating neuropathic pain as a transcriptional switch for repressing and de-repressing endogenous expression of prodynorphin at the spinal level (central sensitization) (19,57,58).…”

“…Glutamate and neuropeptides are neurotransmitters released from the central terminals of dorsal root ganglion (DRG) neurons in the spinal dorsal horn, where signals for different sensory modalities, including pain, are conveyed to higher centers (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Neurotransmitter release is tightly regulated by Ca 2+ -dependent SNARE proteins whose activity is regulated by Ca 2+ -binding proteins (CaBPs) (1,7,13).…”

Post-translational Membrane Insertion of Tail-anchored Transmembrane EF-hand Ca2+ Sensor Calneurons Requires the TRC40/Asna1 Protein Chaperone

“…This is reflected by the broad range of phenomena, including activity-dependent gene transcription, synaptic plasticity, neurotransmitter release, and intracellular trafficking processes that are controlled by Ca 2ϩ transients (1,2). Many different Ca 2ϩ -binding proteins that belong to the EF-hand family of calmodulin (CaM) 4 -like Ca 2ϩ sensors serve as essential regulators of these events.…”

Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

“…-binding proteins that contain the EF-hand, a structural motif annotated for the first time in 1973 in parvalbumin (Kretsinger and Nockolds, 1973;Mikhaylova et al, 2011;Zhou et al, 2013). The canonical EF-hand consists of a Са 2+ -binding loop that contains 12 highly conserved residues flanked by two helices, named as E and F, respectively.…”