Biology subjects

Yogev, S.

Publications and source records attributed to Yogev, S..

2 recordsLinked to original sources

bioRxiv2021

Neurexin and Frizzled signaling intercept axonal-transport at microtubule minus-ends to control synapse formation

Precise synaptic connectivity defines neuronal circuits. Synapse formation is locally determined by transmembrane proteins, yet synaptic material is synthesized remotely and undergoes processive transport in axons. How local synaptogenic signals intercept synaptic cargo in transport to promote its delivery and synapse formation is unknown. We found that control of synaptic cargo delivery at microtubule (MT) minus-ends mediates pro- and anti-synaptogenic activities of presynaptic Neurexin and Frizzled in C. elegans, and identified the atypical kinesin VAB-8/KIF26 as a key molecule in this process. VAB-8/KIF26 levels at synaptic MT minus-ends are controlled by Frizzled and Neurexin, its loss mimics neurexin mutants or Frizzled hyperactivation, and its overexpression can rescue synapse-loss in these backgrounds. VAB-8/KIF26 is required for the synaptic localization of other minus-end proteins and promotes pausing of retrograde transport to allow delivery to synapses. Consistently, reducing retrograde transport rescues synapse-loss in vab-8 and neurexin mutants. These results uncover an important mechanistic link between synaptogenic signaling and axonal transport.

neuroscience↗

bioRxiv2020

Vesicle Navigation of Microtubule Ends Distinguished by A Single Rate-Constant Model

Axonal motor driven cargo utilizes the microtubule cytoskeleton in order to direct cargo, such as presynaptic vesicle precursors, to where they are needed. This transport requires vesicles to travel up to microns in distance. It has recently been observed that finite microtubule lengths can act as roadblocks inhibiting vesicles and increasing the time required for transport. Vesicles reach the end of a microtubule and pause until they can navigate to a neighboring microtubule in order to continue transport. The mechanism by which axonal vesicles navigate the end of a microtubule in order to continue mobility is unknown. In this manuscript we model experimentally observed vesicle pausing at microtubule ends in C. elegans. We show that a single rate-constant model reproduces the time vesicles pause at MT-ends. This model is based on the time a vesicle must detach from its current microtubule and re-attach to a neighboring microtubule. We show that vesicle pause times are different for anterograde and retrograde motion, suggesting that vesicles utilize different proteins at plus and minus end sites. Last, we show that vesicles do not likely utilize a tug-of-war like mechanism and reverse direction in order to navigate microtubule ends.

biophysics↗