Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells

Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells
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DOI:
10.1038/s41598-019-55380-8
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发表时间:
2019-12-23
期刊:
影响因子:
4.6
通讯作者:
Strauss, Olaf
Strauss, Olaf
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barro-Soria, Rene;Caicedo, Alejandro;Strauss, Olaf

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快速、精确和持续的神经传递需要突触前末梢的分级Ca 2+信号。神经递质的释放依赖于一个复杂的相互作用的Ca 2+流量和Ca 2+缓冲突触前终端,这是不完全了解。在这里,我们表明,血管紧张素受体相关蛋白(ATRAP)定位于整个中枢神经系统的突触末梢。在视网膜光感受器突触和小脑苔藓纤维-颗粒细胞突触中,我们发现ATRAP参与了去极化诱发的突触钙瞬变的产生。与野生型相比,在急性分离的制备的视网膜和小脑的ATRAP基因敲除小鼠的钙离子成像揭示了显着减少的肌内质网(SR)钙ATP酶(SERCA)的活性。因此,除了其在血管紧张素信号传导中的常规作用外,ATRAP还调节中枢神经系统内的突触前Ca 2+信号传导。
Fast, precise and sustained neurotransmission requires graded Ca2+ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca2+ fluxes and Ca2+ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca2+ transients. Compared to wild type, Ca2+ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca2+ signaling within the central nervous system.