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bioRxiv · 10.1101/484683

UNC-16/JIP3 inhibits the function of the regeneration promoting isoform of DLK-1

Kulkarni, S. S.·Sheoran, S.·Matsumoto, K.·Hisamoto, N.·Koushika, S. P.
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Abstract

Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. UNC-16, a C. elegans JIP3 homologue, inhibits axonal regeneration by regulating regrowth initiation and rate of regrowth. UNC-16/JIP3 inhibits the regeneration promoting activity of DLK-1 long but acts additively to and independently of inhibitory DLK-1 short isoform. UNC-16/JIP3 promotes DLK-1 punctate localization in a concentration dependent manner limiting DLK-1 long availability at the cut site minutes after injury. UNC-16 negatively regulates actin dynamics dependent on DLK-1 and microtubule dynamics independent of DLK-1. The faster regeneration seen in unc-16 does not lead to functional recovery. We propose a model where UNC-16/JIP3 plays its inhibitory role through tight temporal and spatial control of DLK-1 function. The dual inhibitory control by both UNC-16 and DLK-1 short calibrate the intrinsic growth promoting function of DLK-1 long in vivo.

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Kulkarni, S. S., Sheoran, S., Matsumoto, K., Hisamoto, N., Koushika, S. P.. 2018-12-02. UNC-16/JIP3 inhibits the function of the regeneration promoting isoform of DLK-1. https://doi.org/10.1101/484683

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