Identification of key structural elements for neuronal calcium sensor-1 function in the regulation of the temperature-dependency of locomotion in C. elegans

Martin, Victoria M, Johnson, James R ORCID: 0000-0002-8849-0993, Haynes, Lee P ORCID: 0000-0002-1296-0338, Barclay, Jeff W and Burgoyne, Robert D ORCID: 0000-0002-9219-0387 (2013) Identification of key structural elements for neuronal calcium sensor-1 function in the regulation of the temperature-dependency of locomotion in C. elegans. MOLECULAR BRAIN, 6 (1). 39-.

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Abstract

<h4>Background</h4>Intracellular Ca2+ regulates many aspects of neuronal function through Ca2+ binding to EF hand-containing Ca2+ sensors that in turn bind target proteins to regulate their function. Amongst the sensors are the neuronal calcium sensor (NCS) family of proteins that are involved in multiple neuronal signalling pathways. Each NCS protein has specific and overlapping targets and physiological functions and specificity is likely to be determined by structural features within the proteins. Common to the NCS proteins is the exposure of a hydrophobic groove, allowing target binding in the Ca2+-loaded form. Structural analysis of NCS protein complexes with target peptides has indicated common and distinct aspects of target protein interaction. Two key differences between NCS proteins are the size of the hydrophobic groove that is exposed for interaction and the role of their non-conserved C-terminal tails.<h4>Results</h4>We characterised the role of NCS-1 in a temperature-dependent locomotion assay in C. elegans and identified a distinct phenotype in the ncs-1 null in which the worms do not show reduced locomotion at actually elevated temperature. Using rescue of this phenotype we showed that NCS-1 functions in AIY neurons. Structure/function analysis introducing single or double mutations within the hydrophobic groove based on information from characterised target complexes established that both N- and C-terminal pockets of the groove are functionally important and that deletion of the C-terminal tail of NCS-1 did not impair its ability to rescue.<h4>Conclusions</h4>The current work has allowed physiological assessment of suggestions from structural studies on the key structural features that underlie the interaction of NCS-1 with its target proteins. The results are consistent with the notion that full length of the hydrophobic groove is required for the regulatory interactions underlying NCS-1 function whereas the C-terminal tail of NCS-1 is not essential. This has allowed discrimination between two potential modes of interaction of NCS-1 with its targets.

Item Type:	Article
Additional Information:	Published 27 August 2013.
Uncontrolled Keywords:	Calcium signalling, Calcium binding proteins, C. elegans, NCS-1
Depositing User:	Symplectic Admin
Date Deposited:	10 Nov 2014 15:16
Last Modified:	15 Dec 2022 21:56
DOI:	10.1186/1756-6606-6-39
Publisher's Statement :	© 2013 Martin et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2001000

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