Improved calcium sensor GCaMP-X overcomes the calcium channel perturbations induced by the calmodulin in GCaMP.

ABSTRACT: GCaMP, one popular type of genetically-encoded Ca²⁺ indicator, has been associated with various side-effects. Here we unveil the intrinsic problem prevailing over different versions and applications, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (Ca_V1). GCaMP acts as an impaired apoCaM and Ca²⁺/CaM, both critical to Ca_V1, which disrupts Ca²⁺ dynamics and gene expression. We then design and implement GCaMP-X, by incorporating an extra apoCaM-binding motif, effectively protecting Ca_V1-dependent excitation-transcription coupling from perturbations. GCaMP-X resolves the problems of detrimental nuclear accumulation, acute and chronic Ca²⁺ dysregulati

SUBMITTER: Yang Y 

PROVIDER: S-EPMC5904127 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature