論文 - 詳細
| RRC ID | 75992 |
|---|---|
| 著者 | Kulkarni SS, Sabharwal V, Sheoran S, Basu A, Matsumoto K, Hisamoto N, Ghosh-Roy A, Koushika SP. |
| タイトル | UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons. |
| ジャーナル | 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. |
| 巻・号 | 219(3) |
| 公開日 | 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 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2807 tm4024 |