細胞動態とマウス行動におけるガイダンス受容体システムの役割

抄録

During neural development, guidance molecules such as semaphorins and netrin play crucial roles in neuronal network formation by controlling axonal pathfinding. Semaphorin4A (Sema4A), a member of class 4 semaphorin induced growth cone collapse of hippocampal neurons. The binding of Sema4A to the growth cone indicated the presence of a receptor transmitting signals to intracellular effectors to induce growth cone collapse of hippocampal neurons (Yukawa K et al. Int J Mol Med 16: 115-118, 2005). Transfection experiments of receptor candidate genes into Cos7 cells demonstrated that Sema4A could bind to guidance receptors including Plexin-B1, Plexin-B2 and Plexin-B3. To identify functional Sema4A receptor and the signal transduction machinery, we performed Cos7 cell contraction assay where the completion of intracellular signal transmission induced contraction of Cos7 cells. Expression vectors for receptor candidate genes and Rho family GTPase (Rnd1, Rnd2 or Rnd3) were transfected into Cos7 cells. As a result, we confirmed that Plexin-B1 could transmit intracellular signal of Sema4A through Rnd1. Our data also suggested that Plexin-B2 and B3 could transmit intracellular signal of Sema4A through Rho family GTPase different from Rnd1. Concomitantly, our mouse behavioral analyses now screen knockout mice of semaphorins and guidance receptors to get a clue whether the guidance receptor system controls mouse behavior. The screening disclosed a hyperactive behavior of knockout mice of Sema4D, another class 4 semaphorin. [J Physiol Sci. 2006;56 Suppl:S214]