| RRC ID |
75992
|
| Author |
Kulkarni SS, Sabharwal V, Sheoran S, Basu A, Matsumoto K, Hisamoto N, Ghosh-Roy A, Koushika SP.
|
| Title |
UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.
|
| Journal |
Genetics
|
| Abstract |
Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. Our study shows that UNC-16, a Caenorhabditis elegans JIP3 homolog, inhibits axonal regeneration by regulating initiation and rate of regrowth. This occurs through the inhibition of the regeneration-promoting activity of the long isoform of DLK-1 and independently of the inhibitory short isoform of DLK-1. We show that UNC-16 promotes DLK-1 punctate localization in a concentration-dependent manner limiting the availability of the long isoform of DLK-1 at the cut site, minutes after injury. UNC-16 negatively regulates actin dynamics through DLK-1 and microtubule dynamics partially via DLK-1. We show that post-injury cytoskeletal dynamics in unc-16 mutants are also partially dependent on CEBP-1. The faster regeneration seen in unc-16 mutants does not lead to functional recovery. Our data suggest that the inhibitory control by UNC-16 and the short isoform of DLK-1 balances the intrinsic growth-promoting function of the long isoform of DLK-1 in vivo. We propose a model where UNC-16's inhibitory role in regeneration occurs through both a tight temporal and spatial control of DLK-1 and cytoskeletal dynamics.
|
| Volume |
219(3)
|
| Published |
2021-11-5
|
| DOI |
10.1093/genetics/iyab139
|
| PII |
6359182
|
| PMID |
34740241
|
| PMC |
PMC8570795
|
| MeSH |
Actins / metabolism
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Animals, Genetically Modified
Caenorhabditis elegans / physiology*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
MAP Kinase Kinase Kinases / metabolism*
Microtubules / metabolism
Models, Animal
Mutation
Nerve Regeneration*
Neurons / physiology*
Protein Isoforms / metabolism
Spatio-Temporal Analysis
|
| Resource |
| C.elegans |
tm2807
tm4024 |
