Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein
| Autoři | |
|---|---|
| Rok publikování | 2024 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | EMBO Journal |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.embopress.org/doi/full/10.1038/s44318-024-00254-7 |
| Doi | http://dx.doi.org/10.1038/s44318-024-00254-7 |
| Klíčová slova | Dishevelled 3; Polyglutamylation; TTLL11; Noncanonical Wnt Signaling; Protein Condensates |
| Přiložené soubory | |
| Popis | Polyglutamylation is a reversible posttranslational modification that is catalyzed by enzymes of the tubulin tyrosine ligase-like (TTLL) family. Here, we found that TTLL11 generates a previously unknown type of polyglutamylation that is initiated by the addition of a glutamate residue to the free C-terminal carboxyl group of a substrate protein. TTLL11 efficiently polyglutamylates the Wnt signaling protein Dishevelled 3 (DVL3), thereby changing the interactome of DVL3. Polyglutamylation increases the capacity of DVL3 to get phosphorylated, to undergo phase separation, and to act in the noncanonical Wnt pathway. Both carboxy-terminal polyglutamylation and the resulting reduction in phase separation capacity of DVL3 can be reverted by the deglutamylating enzyme CCP6, demonstrating a causal relationship between TTLL11-mediated polyglutamylation and phase separation. Thus, C-terminal polyglutamylation represents a new type of posttranslational modification, broadening the range of proteins that can be modified by polyglutamylation and providing the first evidence that polyglutamylation can modulate protein phase separation. |
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