| RRC ID |
59438
|
| 著者 |
Andrusiak MG, Sharifnia P, Lyu X, Wang Z, Dickey AM, Wu Z, Chisholm AD, Jin Y.
|
| タイトル |
Inhibition of Axon Regeneration by Liquid-like TIAR-2 Granules.
|
| ジャーナル |
Neuron
|
| Abstract |
Phase separation into liquid-like compartments is an emerging property of proteins containing prion-like domains (PrLDs), yet the in vivo roles of phase separation remain poorly understood. TIA proteins contain a C-terminal PrLD, and mutations in the PrLD are associated with several diseases. Here, we show that the C. elegans TIAR-2/TIA protein functions cell autonomously to inhibit axon regeneration. TIAR-2 undergoes liquid-liquid phase separation in vitro and forms granules with liquid-like properties in vivo. Axon injury induces a transient increase in TIAR-2 granule number. The PrLD is necessary and sufficient for granule formation and inhibiting regeneration. Tyrosine residues within the PrLD are important for granule formation and inhibition of regeneration. TIAR-2 is also serine phosphorylated in vivo. Non-phosphorylatable TIAR-2 variants do not form granules and are unable to inhibit axon regeneration. Our data demonstrate an in vivo function for phase-separated TIAR-2 and identify features critical for its function in axon regeneration.
|
| 巻・号 |
104(2)
|
| ページ |
290-304.e8
|
| 公開日 |
2019-10-23
|
| DOI |
10.1016/j.neuron.2019.07.004
|
| PII |
S0896-6273(19)30602-6
|
| PMID |
31378567
|
| PMC |
PMC6813885
|
| MeSH |
Animals
Axons / metabolism*
Axons / physiology
Caenorhabditis elegans
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Cell Compartmentation
Cytoplasmic Granules
Nerve Regeneration / physiology*
Protein Domains
RNA Recognition Motif Proteins / genetics
RNA Recognition Motif Proteins / metabolism*
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
T-Cell Intracellular Antigen-1 / genetics
T-Cell Intracellular Antigen-1 / metabolism
|
| IF |
14.403
|
| 引用数 |
6
|
| リソース情報 |
| 線虫 |
tm2923
tm361
tm2262 |
