UNC-16/JIP3 negatively regulates actin dynamics dependent on DLK-1 and microtubule dynamics independent of DLK-1 in regenerating neurons

Sucheta S. Kulkarni; Vidur Sabharwal; Seema Sheoran; Atrayee Basu; Kunihiro Matsumoto; Naoki Hisamoto; Anindya Ghosh‐Roy; Sandhya Padmanabhan Koushika

doi:10.1101/484683

NeurosciencebioRxivNov 18, 2019

Preprint

UNC-16/JIP3 negatively regulates actin dynamics dependent on DLK-1 and microtubule dynamics independent of DLK-1 in regenerating neurons

Sucheta S. Kulkarni, Vidur Sabharwal iD, Seema Sheoran iD, Atrayee Basu iD, Kunihiro Matsumoto iD, Naoki Hisamoto iD, Anindya Ghosh‐Roy iD, Sandhya Padmanabhan Koushika iD

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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