Takahashi T, Strittmatter S M
Department of Neurology and, Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA
Neuron. 2001 Feb;29(2):429-39. doi: 10.1016/s0896-6273(01)00216-1.
Semaphorin 3A (Sema3A) binds to neuropilin-1 (NP1) and activates the transmembrane Plexin to transduce a repulsive axon guidance signal. Here, we show that Sema3 signals are transduced equally effectively by PlexinA1 or PlexinA2, but not by PlexinA3. Deletion analysis of the PlexinA1 ectodomain demonstrates that the sema domain prevents PlexinA1 activation in the basal state. Sema-deleted PlexinA1 is constitutively active, producing cell contraction, growth cone collapse, and inhibition of neurite outgrowth. The sema domain of PlexinA1 physically associates with the remainder of the PlexinA1 ectodomain and can reverse constitutive activation. Both the sema portion and the remainder of the ectodomain of PlexinA1 associate with NP1 in a Sema3A-independent fashion. Plexin A1 is autoinhibited by its sema domain, and Sema3A/NP1 releases this inhibition.
信号素3A（Sema3A）与神经纤毛蛋白-1（NP1）结合并激活跨膜丛状蛋白以转导排斥性轴突导向信号。在此，我们表明Sema3信号由丛状蛋白A1或丛状蛋白A2同等有效地转导，但不由丛状蛋白A3转导。对丛状蛋白A1胞外域的缺失分析表明，信号素结构域在基础状态下阻止丛状蛋白A1激活。缺失信号素的丛状蛋白A1组成型激活，导致细胞收缩、生长锥塌陷和神经突生长抑制。丛状蛋白A1的信号素结构域与丛状蛋白A1胞外域的其余部分物理结合，并可逆转组成型激活。丛状蛋白A1胞外域的信号素部分和其余部分均以不依赖Sema3A的方式与NP1结合。丛状蛋白A1被其信号素结构域自身抑制，而Sema3A/NP1解除这种抑制。
