Dynamic control of beta 1 integrin adhesion by the plexinD1-sema3E axis

作者：Choi Young I; Duke Cohan Jonathan S; Chen Wei; Liu Baoyu; Rossy Jeremie; Tabarin Thibault; Ju Lining; Gui Jingang; Gaus Katharina; Zhu Cheng; Reinherz Ellis L^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(1): 379-384.

DOI：10.1073/pnas.1314209111

• thymocyte development
• mechanobiology
• integrin activation
• autoimmunity
• central tolerance

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 beta 1 integrin adhesion domains in cis, whereas its ligation by sema3E in trans regulates individual beta 1 integrin catch bonds. Loss of plexinD1 expression reduces beta 1 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.

• 出版日期2014-1-7