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

• 成果类型: Article
• 署名作者: Rizalar, Filiz Sila; Lucht, Max T.; Petzoldt, Astrid; Kong, Shuhan; Sun, Jiachen; Vines, James H.; Telugu, Narasimha Swamy; Diecke, Sebastian; Kaas, Thomas; Bullmann, Torsten; Schmied, Christopher; Loewe, Delia; King, Jason S.; Cho, Wonhwa; Hallermann, Stefan; Puchkov, Dmytro; Sigrist, Stephan J.; Haucke, Volker
• 署名单位: Free University of Berlin; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; University of Sheffield; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Leipzig University; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11871
• DOI: 10.1126/science.adg1075
• 发表日期: 2023-10-13
• 页码: 223-229
• 关键词: active zone; synaptic vesicles; kinesin; unc-104; protein; TRAFFICKING; mechanisms; MOVEMENT

摘要

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)P-2] 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)P-2 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.