RRC ID 77277
Author Bremer J, Marsden KC, Miller A, Granato M.
Title The ubiquitin ligase PHR promotes directional regrowth of spinal zebrafish axons.
Journal Commun Biol
Abstract To reconnect with their synaptic targets, severed axons need to regrow robustly and directionally along the pre-lesional trajectory. While mechanisms directing axonal regrowth are poorly understood, several proteins direct developmental axon outgrowth, including the ubiquitin ligase PHR (Mycbp2). Invertebrate PHR also limits regrowth of injured axons, whereas its role in vertebrate axonal regrowth remains elusive. Here we took advantage of the high regrowth capacity of spinal zebrafish axons and observed robust and directional regrowth following laser transection of spinal Mauthner axons. We found that PHR directs regrowing axons along the pre-lesional trajectory and across the transection site. At the transection site, initial regrowth of wild-type axons was multidirectional. Over time, misdirected sprouts were corrected in a PHR-dependent manner. Ablation of cyfip2, known to promote F-actin-polymerization and pharmacological inhibition of JNK reduced misdirected regrowth of PHR-deficient axons, suggesting that PHR controls directional Mauthner axonal regrowth through cyfip2- and JNK-dependent pathways.
Volume 2
Pages 195
Published 2019-1-1
DOI 10.1038/s42003-019-0434-2
PII 434
PMID 31149640
PMC PMC6531543
MeSH Actins / metabolism Adaptor Proteins, Signal Transducing / metabolism* Alleles Animals Animals, Genetically Modified Axons / metabolism* Cadherins / metabolism Cytoplasmic Dyneins / metabolism Disease Models, Animal Green Fluorescent Proteins / metabolism Image Processing, Computer-Assisted Ligases / metabolism MAP Kinase Kinase 4 / metabolism Mixed Function Oxygenases / metabolism* Mutation Nerve Regeneration* Neuronal Outgrowth* Spinal Cord / pathology Spinal Cord Injuries / metabolism Transgenes Ubiquitin / metabolism Zebrafish Zebrafish Proteins / metabolism*
IF 4.165