PT  - JOURNAL ARTICLE
AU  - Yaxiong Yang
AU  - Min Liu
AU  - Nan Liu
AU  - Wenxiang Li
AU  - Zhen Yu
AU  - Weili Hong
AU  - Ping Li
AU  - He Jiang
AU  - Haiyan Ge
AU  - Ping Wang
AU  - Sen Song
AU  - Xiaomei Li
AU  - Yubo Fan
AU  - Xiaodong Liu
TI  - Opposing neural signals of Ca<sub>V</sub>1-encoded peptides are tuned by C-terminus mediated inhibition
AID  - 10.1101/2020.01.26.920348
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.26.920348
4099  - http://biorxiv.org/content/early/2020/01/27/2020.01.26.920348.short
4100  - http://biorxiv.org/content/early/2020/01/27/2020.01.26.920348.full
AB  - L-type calcium (CaV1) channels regulate gene expressions via the cascade of excitation-transcription coupling, or directly as standalone CCAT (Calcium Channel Associated Transcriptional-regulator) peptides encoding distal carboxyl-terminus (DCT) of CaV1, both evidenced in dendritogenesis signaling in neurons. We here discover that DCT peptides opposedly mediate these two sets of transcription signals, all tunable in accordance to C-terminus mediated inhibition (CMI) of Ca2+/CaV1 influx. By electrophysiology, neurite morphology, and FRET 2-hybrid binding analyses, we systematically examined native and derived DCT peptides across CaV1, unveiling that the overall balance between cytosolic inhibition versus nuclear facilitation is spatially and temporally tuned by CMI of each DCT variant. Our findings not only resolve several controversies existing to DCT variants, but also propose a de novo scheme of CaV1-centric gene regulation: two concurrent routes of transcription signals initiated from either membrane CaV1 channels or nuclear CaV1-encoded peptides are subject to autonomous feedback tuning by peptide/channel interactions.