CaBP1 regulates Cav1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons

Mol Cell Neurosci. 2018 Apr;88:342-352. doi: 10.1016/j.mcn.2018.03.005. Epub 2018 Mar 13.

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 Cav 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 Cav1 (L-type) channels, Cav1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Cav1 channels to downstream signaling pathways was also disrupted in C-KO SGNs. Activity-dependent repression of neurite growth was significantly blunted and unresponsive to Cav1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Cav1-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 Cav1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.

Keywords: Auditory; Ca(2+) channels; Neurite growth; Spiral ganglion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Caveolin 1 / metabolism
  • Mice
  • Neurites / metabolism*
  • Neurogenesis / physiology
  • Neurons / metabolism*
  • Signal Transduction / physiology
  • Spiral Ganglion / cytology*

Substances

  • Calcium-Binding Proteins
  • Cav1 protein, mouse
  • Caveolin 1
  • Ca2+-binding protein-1
  • Calcium