Endogenous oligomer formation underlies DVL2 condensates and
promotes Wnt/β-catenin signaling

J 2024

Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling

NTOURMAS, Senem; Martin SACHS; Petra PACLÍKOVÁ; Martina BRÜCKNER; Vítězslav BRYJA et al.

Základní údaje

Originální název

Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling

Autoři

NTOURMAS, Senem; Martin SACHS; Petra PACLÍKOVÁ; Martina BRÜCKNER; Vítězslav BRYJA; Jürgen BEHRENS a Dominic B. BERNKOPF

Vydání

eLife, eLife Sciences Publications, Ltd, 2024, 2050-084X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.400 v roce 2023

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00139763

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.7554/eLife.96841

UT WoS

001459215900001

Klíčová slova anglicky

biochemistry; biomolecular condensates; cell biology; chemical biology; dishevelled; DVL2; human; paralogs; Wnt signaling

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 6. 2025 12:49, Mgr. Petra Trembecká, Ph.D.

Anotace

V originále

Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.

Návaznosti

GA22-25365S, projekt VaV

Název: Porozumění funkce Dishevelled v jednotlivých buněčných kompartmentech

Investor: Grantová agentura ČR, Porozumění funkce Dishevelled v jednotlivých buněčných kompartmentech

Citovat

NTOURMAS, Senem; Martin SACHS; Petra PACLÍKOVÁ; Martina BRÜCKNER; Vítězslav BRYJA; Jürgen BEHRENS a Dominic B. BERNKOPF. Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling. eLife. eLife Sciences Publications, Ltd, 2024, roč. 13, December, s. 1-21. ISSN 2050-084X. Dostupné z: https://doi.org/10.7554/eLife.96841.

@article{2485315,
   author = {Ntourmas, Senem and Sachs, Martin and Paclíková, Petra and Brückner, Martina and Bryja, Vítězslav and Behrens, Jürgen and Bernkopf, Dominic B.},
   article_number = {December},
   doi = {https://doi.org/10.7554/eLife.96841},
   keywords = {biochemistry; biomolecular condensates; cell biology; chemical biology; dishevelled; DVL2; human; paralogs; Wnt signaling},
   language = {eng},
   issn = {2050-084X},
   journal = {eLife},
   title = {Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling},
   url = {https://doi.org/10.7554/eLife.96841.3},
   volume = {13},
   year = {2024}
}

TY  - JOUR
ID  - 2485315
AU  - Ntourmas, Senem - Sachs, Martin - Paclíková, Petra - Brückner, Martina - Bryja, Vítězslav - Behrens, Jürgen - Bernkopf, Dominic B.
PY  - 2024
TI  - Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling
JF  - eLife
VL  - 13
IS  - December
SP  - 1-21
EP  - 1-21
PB  - eLife Sciences Publications, Ltd
SN  - 2050084X
KW  - biochemistry
KW  - biomolecular condensates
KW  - cell biology
KW  - chemical biology
KW  - dishevelled
KW  - DVL2
KW  - human
KW  - paralogs
KW  - Wnt signaling
UR  - https://doi.org/10.7554/eLife.96841.3
N2  - Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.
ER  -

NTOURMAS, Senem; Martin SACHS; Petra PACLÍKOVÁ; Martina BRÜCKNER; Vítězslav BRYJA; Jürgen BEHRENS a Dominic B. BERNKOPF. Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling. \textit{eLife}. eLife Sciences Publications, Ltd, 2024, roč.~13, December, s.~1-21. ISSN~2050-084X. Dostupné z: https://doi.org/10.7554/eLife.96841.

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