Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function
Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function
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DOI：
10.1038/nn1320
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发表时间：
2004-10-01
影响因子：
25
通讯作者：
Palczewski, K
中科院分区：
文献类型：
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作者：
Haeseleer, F;Imanishi, Y;Palczewski, K
CaBP1-8 是神经元 Ca2+ 结合蛋白，与钙调蛋白 (CaM) 相似。在这里，我们表明 CaBP4 在光感受器中特异性表达，定位于突触末端。 Cbp4(-/-) 小鼠的外丛状层（包含具有次级神经元的光感受器突触）比对照小鼠更薄。 Cbp4(-/-) 视网膜还具有源自视杆双极细胞和水平细胞的异位突触，异质突触延伸到外核层。 Cbp4(-/-) 杆状双极的反应灵敏度降低了约 100 倍。视网膜电图（ERG）显示视锥细胞和视杆细胞突触功能下降。 Cbp4(-/-)小鼠的表型与不完全先天性静止性夜盲症(CSNB2)患者有相似之处。 CaBP4 直接与 Ca(v)1.4 α(1) 亚基的 C 端结构域相关，并将转染细胞中 Ca(v)1.4 的激活转变为超极化电压。这些观察结果表明，CaBP4 对正常突触功能很重要，可能是通过调节光感受器突触末端的 Ca2+ 流入和神经递质释放来实现的。
CaBP1-8 are neuronal Ca2+-binding proteins with similarity to calmodulin (CaM). Here we show that CaBP4 is specifically expressed in photoreceptors, where it is localized to synaptic terminals. The outer plexiform layer, which contains the photoreceptor synapses with secondary neurons, was thinner in the Cabp4(-/-) mice than in control mice. Cabp4(-/-) retinas also had ectopic synapses originating from rod bipolar and horizontal cells tha HJt extended into the outer nuclear layer. Responses of Cabp4(-/-) rod bipolars were reduced in sensitivity about 100-fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic function. The phenotype of Cabp4(-/-) mice shares similarities with that of incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly associated with the C-terminal domain of the Ca(v)1.4 alpha(1)-subunit and shifted the activation of Ca(v)1.4 to hyperpolarized voltages in transfected cells. These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca2+ influx and neurotransmitter release in photoreceptor synaptic terminals.