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Title: | GPC3-Unc5 receptor complex structure and role in cell migration |
Author: | Akkermans, Onno Delloye-Bourgeois, Céline Peregrina, Claudia Carrasquero Ordaz, Maria Kokolaki, Maria Berbeira Santana, Miguel Chavent, Matthieu Reynaud, Florie Raj, Ritu Agirre, Jon Aksu, Metin S. White, Eleanor Lowe, Edward Ben Amar, Dounia Zaballa, Sofía Huo, Jiandong Pakos, Irene McCubbin, Patrick Comoletti, Davide Owens, Raymond J. Robinson, Carol V. Castellani, Valérie Del Toro, Daniel Seiradake, Elena |
Keywords: | Migració cel·lular Escorça cerebral Cristal·lografia Ressonància de plasmons superficials Cell migration Cerebral cortex Crystallography Surface plasmon resonance |
Issue Date: | 13-Oct-2022 |
Publisher: | Cell Press |
Abstract: | Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.cell.2022.09.025 |
It is part of: | Cell, 2022, vol. 185, num. 1, p. 3931-3949 |
URI: | http://hdl.handle.net/2445/194492 |
Related resource: | https://doi.org/10.1016/j.cell.2022.09.025 |
ISSN: | 0092-8674 |
Appears in Collections: | Articles publicats en revistes (Institut de Neurociències (UBNeuro)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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