小柯机器人

美国加州大学Robert H. Edwards研究团发现接头蛋白AP-3产生突触囊泡(SVs)，通过募集磷脂翻转酶ATP8A1以高频率释放。2023年9月18日，国际知名学术期刊《自然—神经科学》发表了这一成果。

小鼠海马神经元和切片中显示，接头蛋白AP-3制造了一个对高频刺激有特异性反应的SVs亚群。神经递质转运体以不同的比例进入这些SV，导致在不同的兴奋性突触观察到不同的释放特性。

蛋白质组学表明，AP-3靶向磷脂翻转酶ATP8A1到SVs。ATP8A1的缺失再现了与AP-3缺失一起观察到的SV高频动员缺陷。其机制涉及由ATP8A1易位的细胞质取向磷脂酰丝氨酸募集突触素。因此，ATP8A1使AP-3产生的SV子集以高频释放。

研究人员表示神经系统以动作电位的频率编码信息，然后通过突触传递解码。然而，神经递质的快速、同步释放会消耗SV，限制了高放电速率下的释放。那么突触是如何传递频率信息的仍然未知。

附：英文原文

Title: Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1

Author: Xu, Hongfei, Oses-Prieto, Juan A., Khvotchev, Mikhail, Jain, Shweta, Liang, Jocelyn, Burlingame, Alma, Edwards, Robert H.

Issue&Volume: 2023-09-18

Abstract: Neural systems encode information in the frequency of action potentials, which is then decoded by synaptic transmission. However, the rapid, synchronous release of neurotransmitters depletes synaptic vesicles (SVs), limiting release at high firing rates. How then do synapses convey information about frequency Here, we show in mouse hippocampal neurons and slices that the adaptor protein AP-3 makes a subset of SVs that respond specifically to high-frequency stimulation. Neurotransmitter transporters slot onto these SVs in different proportions, contributing to the distinct properties of release observed at different excitatory synapses. Proteomics reveals that AP-3 targets the phospholipid flippase ATP8A1 to SVs; loss of ATP8A1 recapitulates the defect in SV mobilization at high frequency observed with loss of AP-3. The mechanism involves recruitment of synapsin by the cytoplasmically oriented phosphatidylserine translocated by ATP8A1. Thus, ATP8A1 enables the subset of SVs made by AP-3 to release at high frequency.

DOI: 10.1038/s41593-023-01434-0

Source: https://www.nature.com/articles/s41593-023-01434-0

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex