Structural basis of semaphorin-plexin cis interaction

TY - JOUR

T1 - Structural basis of semaphorin-plexin cis interaction

AU - Rozbesky, Daniel

AU - Verhagen, Marieke G.

AU - Karia, Dimple

AU - Nagy, Gergely N.

AU - Alvarez, Luis

AU - Robinson, Ross A.

AU - Harlos, Karl

AU - Padilla-Parra, Sergi

AU - Pasterkamp, R. Jeroen

AU - Jones, Edith Yvonne

PY - 2020/7/1

Y1 - 2020/7/1

N2 - 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.

AB - 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.

KW - axon guidance

KW - cis interaction

KW - plexin

KW - semaphorin

KW - semaphorin signalling

UR - https://www.scopus.com/pages/publications/85085914454

U2 - 10.15252/embj.2019102926

DO - 10.15252/embj.2019102926

M3 - Article

C2 - 32500924

AN - SCOPUS:85085914454

SN - 0261-4189

VL - 39

JO - EMBO Journal

JF - EMBO Journal

IS - 13

M1 - e102926

ER -