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CaBP1 regulates Ca(v)1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons
Journal article   Open access   Peer reviewed

CaBP1 regulates Ca(v)1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons

Tian Yang, Ji-Eun Choi, Daniel Soh, Kevin Tobin, Mei-ling Joiner, Marlan Hansen and Amy Lee
Molecular and cellular neurosciences, Vol.88, pp.342-352
04/01/2018
DOI: 10.1016/j.mcn.2018.03.005
PMCID: PMC6013052
PMID: 29548764
url
https://www.ncbi.nlm.nih.gov/pmc/articles/6013052View
Open Access

Abstract

CaBP1 is a Ca2+ binding protein that is widely expressed in neurons in the brain, retina, and cochlea. In heterologous expression systems, CaBP1 interacts with and regulates voltage-gated Ca-v Ca2+ channels but whether this is the case in neurons is unknown. Here, we investigated the cellular functions of CaBP1 in cochlear spiral ganglion neurons (SGNs), which express high levels of CaBP1. Consistent with the role of CaBP1 as a suppressor of Ca2+-dependent inactivation (CDI) of Ca(v)1 (L-type) channels, Ca(v)1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Ca(v)1 channels to downstream signaling pathways was also disrupted in C-KO SGNs. Activity-dependent repression of neurite growth was significantly blunted and unresponsive to Ca(v)1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Ca(v)1-mediated Ca2+ signals and phosphorylation of cAMP-response element binding protein were reduced in C KO SGNs compared to WT SGNs. Our findings establish a role for CaBP1 as an essential regulator of Ca(v)1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.
Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology

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