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PLoS One. 2016 Aug 30;11(8):e0161414. doi: 10.1371/journal.pone.0161414. eCollection 2016.

Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics.

Author information

1
Department of Stomatology, Xiang Ya Hospital, Central South University, Changsha, Hunan, China.
2
Department of Pharmacology, Yale University, New Haven, Connecticut, United States of America.
3
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America.
4
Yale Comprehensive Cancer Center, New Haven, Connecticut, United States of America.
5
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, United States of America.

Abstract

Neuronal calcium sensor-1 (NCS-1 Var1) is a calcium-binding protein expressed in most tissues. We examined a poorly characterized variant of NCS-1 (Var2), identified only in humans where the N-terminal 22 amino acid residues of native NCS-1(MGKSNSKLKPEVVEELTRKTY) were replaced with 4 different residues (MATI). Because alterations in the level of expression of NCS-1 Var1 and the expression of NCS-1 variants have been correlated with several neurological diseases, the relative expression and functional role of NCS-1 Var2 was examined. We found that NCS-1 Var2 mRNA levels are not found in mouse tissues and are expressed at levels ~1000-fold lower than NCS-1 Var1 in three different human cell lines (SHSY5Y, HEK293, MB231). Protein expression of both variants was only identified in cell lines overexpressing exogenous NCS-1 Var2. The calcium binding affinity is ~100 times weaker in purified NCS-1 Var2 than NCS-1 Var1. Because truncation of NCS-1 Var1 has been linked to functional changes in neurons, we determined whether the differing properties of the NCS-1 variants could potentially contribute to the altered cell function. In contrast to previous reports showing that overexpression of NCS-1 Var1 increases calcium-dependent processes, functional differences in cells overexpressing NCS-1 Var2 were undetectable in assays for cell growth, cell death and drug (paclitaxel) potency. Our results suggest that NCS-1 Var1 is the primary functional version of NCS-1.

PMID:
27575489
PMCID:
PMC5004852
DOI:
10.1371/journal.pone.0161414
[Indexed for MEDLINE]
Free PMC Article

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