Neuronal calcium sensors and synaptic plasticity
Department of Anatomy, MRC Centre for Synaptic Plasticity, University of Bristol, Bristol, UK. Biochemical Society Transactions
(Impact Factor: 3.19).
12/2009; 37(Pt 6):1359-63. DOI: 10.1042/BST0371359
Calcium entry plays a major role in the induction of several forms of synaptic plasticity in different areas of the central nervous system. The spatiotemporal aspects of these calcium signals can determine the type of synaptic plasticity induced, e.g. LTP (long-term potentiation) or LTD (long-term depression). A vast amount of research has been conducted to identify the molecular and cellular signalling pathways underlying LTP and LTD, but many components remain to be identified. Calcium sensor proteins are thought to play an essential role in regulating the initial part of synaptic plasticity signalling pathways. However, there is still a significant gap in knowledge, and it is only recently that evidence for the importance of members of the NCS (neuronal calcium sensor) protein family has started to emerge. The present minireview aims to bring together evidence supporting a role for NCS proteins in plasticity, focusing on emerging roles of NCS-1 and hippocalcin.
Available from: Laetitia Francelle
- "Although the physiological role of hippocalcin is not completely understood, it is implicated in the regulation of neuronal viability and plasticity. Evidences showed that hippocalcin is important for the homeostasis of intracellular calcium levels (Amici et al., 2009). Hippocalcin can protect hippocampal neurons against excitotoxicity induced damage by enhancing Ca 2+ extrusion and maintaining ideal intracellular Ca 2+ levels (Masuo et al., 2007). "
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ABSTRACT: HD is caused by a mutation in the huntingtin gene that consists in a CAG repeat expansion translated into an abnormal poly-glutamine (polyQ) tract in the huntingtin (Htt) protein. The most striking neuropathological finding in HD is the atrophy of the striatum. The regional expression of mutant Htt (mHtt) is ubiquitous in the brain and cannot explain by itself the preferential vulnerability of the striatum in HD. mHtt has been shown to produce an early defect in transcription, through direct alteration of the function of key regulators of transcription and in addition, more indirectly, as a result of compensatory responses to cellular stress. In this review, we focus on gene products that are preferentially expressed in the striatum and have down- or up-regulated expression in HD and, as such, may play a crucial role in the susceptibility of the striatum to mHtt. Many of these striatal gene products are for a vast majority down-regulated and more rarely increased in HD. Recent research shows that some of these striatal markers have a pro-survival/neuroprotective role in neurons (e.g., MSK1, A2A, and CB1 receptors) whereas others enhance the susceptibility of striatal neurons to mHtt (e.g., Rhes, RGS2, D2 receptors). The down-regulation of these latter proteins may be considered as a potential self-defense mechanism to slow degeneration. For a majority of the striatal gene products that have been identified so far, their function in the striatum is unknown and their modifying effects on mHtt toxicity remain to be experimentally addressed. Focusing on these striatal markers may contribute to a better understanding of HD pathogenesis, and possibly the identification of novel therapeutic targets.
Available from: Biao Wang
- "CaM is one such calciumbinding protein that is considered a major transducer of calcium signals. Calcium entry plays a major role in the induction of several forms of synaptic plasticity in different areas of the central nervous system (Amici et al. 2009). LTP induction results in calcium entry via AMPA and NMDA receptors and calcium channels, binding with CaM and then forming a Calcium/CaM complex (Miyamoto 2006) which activates CaMKII through auto-phosphorylation on threonine residue 286 (Fink and Meyer 2002). "
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ABSTRACT: Aluminum-induced neuronal injury has been implicated in various neurodegenerative disorders. How-ever, the underlying mechanism involved in this patho-genesis still remains unknown. Our present findings demonstrated that chronic aluminum exposure resulted in spatial learning impairment and significantly increased intracellular calcium level in the hippocampus of rats. Examination of the associated protein molecules essential for induction and maintenance of long-term potentiation revealed that aluminum exposure could increase the expression level of calmodulin (CaM), but the expression levels of CaM-dependent protein kinase II (CaMKII), and phosphorylated cAMP-responsive element binding protein (CREB) were significantly reduced, whereas the total protein levels of CaMKII and CREB did not change in the aluminum-treated hippocampus. Thus, we provide a pre-viously unrecognized mechanism whereby chronic aluminum exposure impairs hippocampal learning and memory, at least in part, through disruption of intracellular calcium homeostasis and CaM/CaMKII/CREB signaling pathway. Keywords Aluminum exposure Á Calmodulin-dependent protein kinase II Á cAMP-responsive element binding protein Á Morris water maze Á Neurogranin Introduction
Available from: David J Miller
- "Most NCS family members are thought to be multifunctional regulators of neuronal cellular processes , , only NCS-A types being known to function in both neuronal and non-neuronal cell types , , . Whereas NCS-B proteins have neuronal functions in vertebrates, the broad endodermal expression pattern observed for AmAC (Fig. 3) suggests a non-neuronal role during coral development. "
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ABSTRACT: To understand the calcium-mediated signalling pathways underlying settlement and metamorphosis in the Scleractinian coral Acropora millepora, a predicted protein set derived from larval cDNAs was scanned for the presence of EF-hand domains (Pfam Id: PF00036). This approach led to the identification of a canonical calmodulin (AmCaM) protein and an uncharacterised member of the Neuronal Calcium Sensor (NCS) family of proteins known here as Acrocalcin (AmAC). While AmCaM transcripts were present throughout development, AmAC transcripts were not detected prior to gastrulation, after which relatively constant mRNA levels were detected until metamorphosis and settlement. The AmAC protein contains an internal CaM-binding site and was shown to interact in vitro with AmCaM. These results are consistent with the idea that AmAC is a target of AmCaM in vivo, suggesting that this interaction may regulate calcium-dependent processes during the development of Acropora millepora.
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