Zanata Silvio M, Hovatta Iiris, Rohm Beate, Püschel Andreas W
Molecular Neurogenetics Laboratory, Department of Neurochemistry, Max-Planck-Institute for Brain Research, D-60528 Frankfurt, Germany.
J Neurosci. 2002 Jan 15;22(2):471-7. doi: 10.1523/JNEUROSCI.22-02-00471.2002.
The semaphorins are a large protein family that is involved in the patterning of neuronal connections in the developing nervous system of both vertebrates and invertebrates. The chemorepulsive axon guidance signal Semaphorin 3A (Sema3A) induces the depolymerization of actin filaments and the collapse of sensory growth cones by activating a receptor complex that contains a plexin as the signal-transducing subunit. Here we show that, of a large number of GTPases tested, only Rnd1 and RhoD bind the cytoplasmic domain of Plexin-A1. Recruitment of active Rnd1 is sufficient to trigger signaling by Plexin-A1, even in the absence of Sema3A, and initiates cytoskeletal collapse by activating its cytoplasmic domain. RhoD, in contrast, blocks Plexin-A1 activation by Rnd1 and repulsion of sympathetic axons by Sema3A. Thus, the antagonism of two GTPases regulates the activity of the Sema3A receptor, and activation by Rnd1 appears to be an essential step in signaling by Plexin-A1.
信号素是一个大型蛋白质家族，参与脊椎动物和无脊椎动物发育中的神经系统中神经元连接的模式形成。化学排斥性轴突导向信号信号素3A（Sema3A）通过激活一个包含作为信号转导亚基的丛蛋白的受体复合物，诱导肌动蛋白丝解聚和感觉生长锥塌陷。我们在此表明，在大量测试的GTP酶中，只有Rnd1和RhoD与丛蛋白A1的胞质结构域结合。活性Rnd1的募集足以触发丛蛋白A1的信号传导，即使在没有Sema3A的情况下也是如此，并通过激活其胞质结构域引发细胞骨架塌陷。相比之下，RhoD阻断Rnd1对丛蛋白A1的激活以及Sema3A对交感神经轴突的排斥作用。因此，两种GTP酶的拮抗作用调节Sema3A受体的活性，而Rnd1的激活似乎是丛蛋白A1信号传导的一个关键步骤。
