2024-03-28T19:07:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1693652020-12-13T09:15:39Zcom_10261_112com_10261_1col_10261_365
2018-09-04T07:07:34Z
urn:hdl:10261/169365
TMEM59 potentiates Wnt signaling by promoting signalosome formation
Gerlach, Jan P.
Jordens, Ingrid
Tauriello, Daniele V. F.
Land-Kuper, Ineke van 't.
Bugter, Jeroen M.
Noordstra, Ivar
Kooij, Johanneke van der
Low, Teck Y.
Pimentel-Muiños, Felipe X.
Xanthakis, Despina
Fenderico, Nicola
Rabouille, Catherine
Heck, Albert J. R.
Egan, David A.
Maurice, Madelon M.
Ministerio de Economía y Competitividad (España)
Netherlands Organization for Scientific Research
European Commission
European Research Council
Dutch Cancer Society
Frizzled
Signalosome
Wnt signaling
Multimerization
Protein–protein interactions
Wnt/β-catenin signaling controls development and adult tissue homeostasis by regulating cell proliferation and cell fate decisions. Wnt binding to its receptors Frizzled (FZD) and low-density lipoprotein-related 6 (LRP6) at the cell surface initiates a signaling cascade that leads to the transcription of Wnt target genes. Upon Wnt binding, the receptors assemble into large complexes called signalosomes that provide a platform for interactions with downstream effector proteins. The molecular basis of signalosome formation and regulation remains elusive, largely due to the lack of tools to analyze its endogenous components. Here, we use internally tagged Wnt3a proteins to isolate and characterize activated, endogenous Wnt receptor complexes by mass spectrometry-based proteomics. We identify the single-span membrane protein TMEM59 as an interactor of FZD and LRP6 and a positive regulator of Wnt signaling. Mechanistically, TMEM59 promotes the formation of multi-meric Wnt–FZD assemblies via intramembrane interactions. Subsequently, these Wnt–FZD–TMEM59 clusters merge with LRP6 to form mature Wnt signalosomes. We conclude that the assembly of multiprotein Wnt signalosomes proceeds along well-ordered steps that involve regulated intramembrane interactions.
2018-09-04T07:07:34Z
2018-09-04T07:07:34Z
2018
2018-09-04T07:07:34Z
artículo
Proceedings of the National Academy of Sciences 115(17): E3996-E4005 (2018)
http://hdl.handle.net/10261/169365
10.1073/pnas.1721321115
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/501100000780
29632210
eng
Publisher's version
https://doi.org/10.1073/pnas.1721321115
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-53320-R
info:eu-repo/grantAgreement/EC/FP7/608180
info:eu-repo/grantAgreement/EC/H2020/686547
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-88390-R
info:eu-repo/grantAgreement/EC/FP7/242958
https://creativecommons.org/licenses/by-nc-nd/4.0/
openAccess
National Academy of Sciences (U.S.)