Faculty Opinions recommendation of Kinesin-3 Responds to Local Microtubule Dynamics to Target Synaptic Cargo Delivery to the Presynapse.
Year: 2019
Type: peer-review
Abstract: Neurons in the central nervous system establish thousands of en passant synapses along their axons.Robust neurotransmission depends on the replenishment of synaptic components in a spatially precise manner.Using live-cell microscopy and single-molecule reconstitution assays, we find that the delivery of synaptic vesicle precursors (SVPs) to en passant synapses in hippocampal neurons is specified by an interplay between the kinesin-3 KIF1A motor and presynaptic microtubules.Presynaptic sites are hotspots of dynamic microtubules rich in GTP-tubulin.KIF1A binds more weakly to GTP-tubulin than GDP-tubulin and competes with EB proteins for binding to the microtubule plus-end.A disease-causing mutation within KIF1A that reduces preferential binding to GDP-vs.GTP-rich microtubules disrupts SVP delivery and reduces presynaptic release upon neuronal stimulation.Thus, the localized enrichment of dynamic microtubules along the axon specifies a localized unloading zone that ensures the accurate delivery of SVPs, controlling presynaptic strength in hippocampal neurons.
Authors: Stephanie Gupton, Shalini Menon
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4234820711