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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.

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


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.

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