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

Item Type:	Article
Title:	Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly
Creators Name:	Rizalar, F.S. and Lucht, M.T. and Petzoldt, A. and Kong, S. and Sun, J. and Vines, J.H. and Telugu, N.S. and Diecke, S. and Kaas, T. and Bullmann, T. and Schmied, C. and Löwe, D. and King, J.S. and Cho, W. and Hallermann, S. and Puchkov, D. and Sigrist, S.J. and Haucke, V.
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)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.
Keywords:	Axonal Transport, Kinesins, Neurons, Organelles, Synaptic Vesicles
Source:	Science
ISSN:	0036-8075
Publisher:	American Association for the Advancement of Science
Volume:	382
Number:	6667
Page Range:	223-230
Date:	12 October 2023
Official Publication:	https://doi.org/10.1126/science.adg1075
PubMed:	View item in PubMed

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