@article{962be209bf1f447b8b018ff3ce47fa7f,
title = "Structural basis of semaphorin-plexin cis interaction",
abstract = "Semaphorin ligands interact with plexin receptors to contribute to functions in the development of myriad tissues including neurite guidance and synaptic organisation within the nervous system. Cell-attached semaphorins interact in trans with plexins on opposing cells, but also in cis on the same cell. The interplay between trans and cis interactions is crucial for the regulated development of complex neural circuitry, but the underlying molecular mechanisms are uncharacterised. We have discovered a distinct mode of interaction through which the Drosophila semaphorin Sema1b and mouse Sema6A mediate binding in cis to their cognate plexin receptors. Our high-resolution structural, biophysical and in vitro analyses demonstrate that monomeric semaphorins can mediate a distinctive plexin binding mode. These findings suggest the interplay between monomeric vs dimeric states has a hereto unappreciated role in semaphorin biology, providing a mechanism by which Sema6s may balance cis and trans functionalities.",
keywords = "axon guidance, cis interaction, plexin, semaphorin, semaphorin signalling",
author = "Daniel Rozbesky and Verhagen, {Marieke G.} and Dimple Karia and Nagy, {Gergely N.} and Luis Alvarez and Robinson, {Ross A.} and Karl Harlos and Sergi Padilla-Parra and Pasterkamp, {R. Jeroen} and Jones, {Edith Yvonne}",
note = "Funding Information: We thank the staff of Diamond Light Source for support and access to beamlines I03 and I24; Weixian Lu for help with tissue culture; Thomas Walter for crystallisation technical support; David Staunton for assistance with biophysical experiments. The work was funded by Cancer Research UK and Medical Research Council Programme Grants (to E.Y.J., C375/A17721 and MR/M000141/1) and the Netherlands Organization for Scientific Research (to R.J.P., ALW‐VICI). The Wellcome Centre for Human Genetics is supported by Wellcome Trust Centre grant 203141/Z/16/Z. D.R. was supported by EMBO Long‐Term Fellowship (ALTF 604‐2014) and S. P. P. by the Nuffield Department of Medicine Leadership Fellowship. Funding Information: We thank the staff of Diamond Light Source for support and access to beamlines I03 and I24; Weixian Lu for help with tissue culture; Thomas Walter for crystallisation technical support; David Staunton for assistance with biophysical experiments. The work was funded by Cancer Research UK and Medical Research Council Programme Grants (to E.Y.J., C375/A17721 and MR/M000141/1) and the Netherlands Organization for Scientific Research (to R.J.P., ALW-VICI). The Wellcome Centre for Human Genetics is supported by Wellcome Trust Centre grant 203141/Z/16/Z. D.R. was supported by EMBO Long-Term Fellowship (ALTF 604-2014) and S. P. P. by the Nuffield Department of Medicine Leadership Fellowship. Publisher Copyright: {\textcopyright} 2020 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2020",
month = jul,
day = "1",
doi = "10.15252/embj.2019102926",
language = "English",
volume = "39",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "13",
}