Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein
| Authors | |
|---|---|
| Year of publication | 2024 |
| Type | Article in Periodical |
| Magazine / Source | EMBO Journal |
| MU Faculty or unit | |
| Citation | |
| web | https://www.embopress.org/doi/full/10.1038/s44318-024-00254-7 |
| Doi | http://dx.doi.org/10.1038/s44318-024-00254-7 |
| Keywords | Dishevelled 3; Polyglutamylation; TTLL11; Noncanonical Wnt Signaling; Protein Condensates |
| Attached files | |
| Description | 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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