0604464 - BTÚ 2025 RIV US eng J - Journal Article
Kravec, M. - Šedo, O. - Nedvědová, Jana - Micka, M. - Šulcová, M. - Zezula, N. - Gomoryova, K. - Potěšil, D. - Sri Ganji, R. - Bologna, S. - Červenka, I. - Zdráhal, Z. - Harnoš, J. - Tripsianes, K. - Janke, C. - Bařinka, Cyril - Bryja, V.
Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein.
EMBO Journal. Roč. 43, č. 22 (2024), s. 5635-5666. ISSN 0261-4189. E-ISSN 1460-2075
R&D Projects: GA ČR(CZ) GA22-25365S; GA ČR(CZ) GA23-07149S; GA MŠMT LX22NPO5102; GA MŠMT(CZ) EF18_046/0015974
Research Infrastructure: CIISB III - 90242
Institutional support: RVO:86652036
Keywords : planar cell polarity * beta-tubulin * dix domain * wnt * family * Dishevelled 3
OECD category: Biochemistry and molecular biology
Impact factor: 9.5, year: 2023 ; AIS: 4.873, rok: 2023
Method of publishing: Open access
Result website:
https://www.embopress.org/doi/full/10.1038/s44318-024-00254-7DOI: https://doi.org/10.1038/s44318-024-00254-7

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.
Permanent Link: https://hdl.handle.net/11104/0361870