title: Dynamic control of β1 integrin adhesion by the plexinD1-sema3E axis.
abstract: Plexins and semaphorins comprise a large family of receptor-ligand pairs controlling cell guidance in nervous, immune, and vascular systems. How plexin regulation of neurite outgrowth, lymphoid trafficking, and vascular endothelial cell branching is linked to integrin function, central to most directed movement, remains unclear. Here we show that on developing thymocytes, plexinD1 controls surface topology of nanometer-scaled β1 integrin adhesion domains in cis, whereas its ligation by sema3E in trans regulates individual β1 integrin catch bonds. Loss of plexinD1 expression reduces β1 integrin clustering, thereby diminishing avidity, whereas sema3E ligation shortens individual integrin bond lifetimes under force to reduce stability. Consequently, both decreased expression of plexinD1 during developmental progression and a thymic medulla-emanating sema3E gradient enhance thymocyte movement toward the medulla, thus enforcing the orchestrated lymphoid trafficking required for effective immune repertoire selection. Our results demonstrate plexin-tunable molecular features of integrin adhesion with broad implications for many cellular processes.
authors.affiliation: Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115.
authors.forename: Young I
authors.initials: YI
authors.lastname: Choi
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Duke-Cohan
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Baoyu
authors.initials: B
authors.lastname: Liu
authors.forename: Jérémie
authors.initials: J
authors.lastname: Rossy
authors.forename: Thibault
authors.initials: T
authors.lastname: Tabarin
authors.forename: Lining
authors.initials: L
authors.lastname: Ju
authors.forename: Jingang
authors.initials: J
authors.lastname: Gui
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D003598:Cytoskeletal Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins; D039961:Semaphorins; D015398:Signal Transduction; D013269:Stochastic Processes; D060168:Thymocytes / Q000166:cytology*
chemical_list: D001323:Autoantibodies; D015816:Cell Adhesion Molecules, Neuronal; D018925:Chemokines; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D019012:Integrin beta1; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse; C111150:Sema3e protein, mouse; D039961:Semaphorins
keywords: autoimmunity; central tolerance; integrin activation; mechanobiology; thymocyte development