德国莱布尼茨分子药理学研究中心Volker Haucke研究组探明，磷脂酰肌醇3,5-二磷酸[PI(3,5)P₂]促进轴突囊泡运输和突触前组装。相关论文于2023年10月13日发表于国际顶尖学术期刊《科学》杂志上。

他们的研究结果表明，罕见的内体晚期信号脂质磷脂酰肌醇PI(3,5)P₂指导了人类神经元突触囊泡和前体囊泡活性区蛋白的轴突共运输。前体囊泡不同于传统的分泌细胞器、核内体和降解溶酶体，并通过激酶激酶KIF1A同时检测到PI(3,5)P₂和活性ARL8转运到突触前腔室。他们的发现确定了突触囊泡和活性区蛋白向发育中的突触传递的关键机制。

据悉，神经元通过特殊的突触前区室传递信息。与传统的细胞器不同，表征神经元突触前的特殊装置必须从头形成。突触前神经传递的成分是如何运输和组装的，人们知之甚少。

附：英文原文

Title: Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly

Author: Filiz Sila Rizalar, Max T. Lucht, Astrid Petzoldt, Shuhan Kong, Jiachen Sun, James H. Vines, Narasimha Swamy Telugu, Sebastian Diecke, Thomas Kaas, Torsten Bullmann, Christopher Schmied, Delia Lwe, Jason S. King, Wonhwa Cho, Stefan Hallermann, Dmytro Puchkov, Stephan J. Sigrist, Volker Haucke

Issue&Volume: 2023-10-13

Abstract: Neurons relay information via specialized presynaptic compartments for neurotransmission. Unlike conventional organelles, the specialized apparatus characterizing the neuronal presynapse must form de novo. How the components for presynaptic neurotransmission are transported and assembled is poorly understood. Our results show that the rare late endosomal signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] directs the axonal cotransport of synaptic vesicle and active zone proteins in precursor vesicles in human neurons. Precursor vesicles are distinct from conventional secretory organelles, endosomes, and degradative lysosomes and are transported by coincident detection of PI(3,5)P2 and active ARL8 via kinesin KIF1A to the presynaptic compartment. Our findings identify a crucial mechanism that mediates the delivery of synaptic vesicle and active zone proteins to developing synapses.

DOI: adg1075

Source: https://www.science.org/doi/10.1126/science.adg1075