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_v1 (L-type) channels, Ca_v1 currents underwent greater CDI in SGNs from mice lacking CaBP1 (C-KO) than in wild-type (WT) SGNs. The coupling of Ca_v1 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_v1 antagonists in C-KO SGNs in contrast to WT SGNs. Moreover, Ca_v1-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_v1 channels in SGNs and their coupling to downstream pathways controlling activity-dependent transcription and neurite growth.

CaBP1是一种Ca ²⁺结合蛋白，在大脑，视网膜和耳蜗的神经元中广泛表达。在异源表达系统中，CaBP1与电压门控的Ca _v Ca ²⁺通道相互作用并调节电压门控的Ca _v Ca ²⁺通道，但在神经元中是否如此尚不清楚。在这里，我们调查了耳蜗螺旋神经节神经元（SGNs）中的CaBP1的细胞功能，这些神经元表达高水平的CaBP1。与CaBP1作为Ca _v 1（L型）通道的Ca ²⁺依赖性失活（CDI）抑制剂的作用相一致，Ca _v 1电流在缺乏CaBP1（C-KO）的小鼠中的SGNs中比在CGN中受到更大的CDI。野生型（WT）SGN。Ca _v的耦合在C-KO SGNs中，通往下游信号通路的1个通道也被破坏。与WT SGN相比，C-KO SGNs中神经突生长的活动依赖性抑制显着减弱并且对Ca _v 1拮抗剂无反应。此外，与WT SGN相比，C-KO SGNs中Ca _v 1介导的Ca ²⁺信号和cAMP反应元件结合蛋白的磷酸化降低。我们的发现确立了CaBP1作为SGN中Ca _v 1通道的必需调节剂的作用，以及它们与控制活性依赖性转录和神经突生长的下游途径的耦合。