RT Journal Article
SR Electronic
T1 UNC-16/JIP3 inhibits the function of the regeneration promoting isoform of DLK-1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 484683
DO 10.1101/484683
A1 Sucheta S. Kulkarni
A1 Seema Sheoran
A1 Kunihiro Matsumoto
A1 Naoki Hisamoto
A1 Sandhya P. Koushika
YR 2018
UL http://biorxiv.org/content/early/2018/12/04/484683.abstract
AB The extent of neuronal regeneration after injury depends on the genetic control of the intrinsic growth potential of neurons and their extracellular environment. We show that UNC-16, a C. elegans JIP3 (JNK Interacting Protein 3) homologue, plays an inhibitory role after axotomy in the early stages of neuronal regeneration. UNC-16 inhibits the regeneration promoting long isoform of DLK-1, an essential MAPKKK for neuronal regeneration, while acting independently of the inhibitory DLK-1 short isoform. UNC-16 sequesters DLK-1L along the axon in a concentration dependent manner and prevents its accumulation at the cut site immediately after axotomy thereby preventing the early steps in regrowth. The inhibitory control of UNC-16 may provide a general means to control DLK in regenerating neurons.Summary statement Our work demonstrates that the MAPKinase cascade scaffolding protein, UNC-16/JIP3, is a negative regulator of the regeneration promoting MAPKKK DLK isoform.