RT Journal Article
SR Electronic
T1 The guidance and adhesion protein FLRT2 dimerizes <em>in cis</em> via dual Small-X<sub>3</sub>-Small transmembrane motifs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.06.328401
DO 10.1101/2020.10.06.328401
A1 Verity Jackson
A1 Julia Hermann
A1 Christopher J. Tynan
A1 Daniel J. Rolfe
A1 Robin A. Corey
A1 Anna L. Duncan
A1 Maxime Noriega
A1 Amy Chu
A1 Antreas C. Kalli
A1 E. Yvonne Jones
A1 Mark S. P. Sansom
A1 Marisa L. Martin-Fernandez
A1 Elena Seiradake
A1 Matthieu Chavent
YR 2021
UL http://biorxiv.org/content/early/2021/08/02/2020.10.06.328401.abstract
AB Fibronectin Leucine-rich Repeat Transmembrane (FLRT 1-3) proteins are a family of broadly expressed single-spanning transmembrane receptors that play key roles in development. Their extracellular domains mediate homotypic cell-cell adhesion and heterotypic protein interactions with other receptors to regulate cell adhesion and guidance. These in trans FLRT interactions determine the formation of signaling complexes of varying complexity and function. Whether FLRTs also interact at the surface of the same cell, in cis, remains unknown. Here, molecular dynamics simulations reveal two dimerization motifs in the FLRT2 transmembrane helix. Single particle tracking experiments show that these ‘Small-X3-Small’ motifs synergize with a third dimerization motif encoded in the extracellular domain to permit the cis association and co-diffusion patterns of FLRT2 receptors on cells. These results may point to a competitive switching mechanism between in cis and in trans interactions which suggests that homotypic FLRT interaction mirrors the functionalities of classic adhesion molecules.Fields Structural Biology and Biophysics / Computational BiologyCompeting Interest StatementThe authors have declared no competing interest.