Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
GX19-28347X
Czech Science Foundation
GA22-25365S
Czech Science Foundation
GA23-07149S
Czech Science Foundation
GA22-06405S
Czech Science Foundation
ANR-10-IDEX-0001-02
Agence Nationale de la Recherche (ANR)
ANR-12-BSV2-0007
Agence Nationale de la Recherche (ANR)
ANR-17-CE13-0021
Agence Nationale de la Recherche (ANR)
ANR-11-LBX-0038
LabEx Cell&Scale grant
ANR-17-CONV-0005
Institut de convergence Q-life grant
86652036
Czech Academy of Sciences grant RVO
1414120
Charles University Grant Agency
LM2018129
MEYS CR
LM2018127
MEYS CR
CZ.02.1.01/0.0/0.0/18_046/0015974
European Regional Development Fund-Project
INFRA LM2018140
e-Infrastruktura CZ
LX22NPO5102
Funded by the European Union - Next Generation EU - National Institute for Cancer Research
PubMed
39349846
PubMed Central
PMC11574253
DOI
10.1038/s44318-024-00254-7
PII: 10.1038/s44318-024-00254-7
Knihovny.cz E-zdroje
- Klíčová slova
- Dishevelled 3, Noncanonical Wnt Signaling, Polyglutamylation, Protein Condensates, TTLL11,
- MeSH
- fosforylace MeSH
- HEK293 buňky MeSH
- kyselina polyglutamová metabolismus analogy a deriváty MeSH
- lidé MeSH
- peptidsynthasy * metabolismus genetika MeSH
- posttranslační úpravy proteinů * MeSH
- protein dishevelled * metabolismus genetika MeSH
- separace fází MeSH
- signální dráha Wnt MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DVL3 protein, human MeSH Prohlížeč
- kyselina polyglutamová MeSH
- peptidsynthasy * MeSH
- protein dishevelled * MeSH
- tubulin polyglutamylase MeSH Prohlížeč
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.
Central European Institute of Technology Brno Czech Republic
Department of Biochemistry Faculty of Science Charles University Prague Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
Institut Curie Université PSL CNRS UMR3348 Orsay France
Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Vestec Czech Republic
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