Regulation of dendritic branching and spine maturation by semaphorin3A-fyn signaling
Regulation of dendritic branching and spine maturation by semaphorin3A-fyn signaling
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DOI：
10.1523/jneurosci.5453-05.2006
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发表时间：
2006-03-15
影响因子：
5.3
通讯作者：
Goshima, Y
中科院分区：
文献类型：
--
作者：
Morita, A;Yamashita, N;Goshima, Y
semaphorin3A （Sema3A）是信号蛋白家族的一员，在神经系统的发育过程中作为一种化学排斥剂或化学引诱剂作用于各种轴突和树突。我们发现Sema3A在培养的皮质神经元中诱导突触后密度-95 （PSD-95）和突触前突触蛋白1聚集，而不改变脊髓或丝状足的密度。神经肽-1 （NRP-1）是Sema3A的受体，存在于轴突和树突上。当培养的神经元暴露于Sema3A时，PSD-95的簇大小显着增强，PSD-95和NRP-1广泛共定位或富含肌动蛋白的突起。Sema3A对脊柱形态的影响被PP2（一种Src型酪氨酸激酶抑制剂）阻断，而不被PP3（一种非活性相关化合物）阻断。在培养的fyn（-/-）小鼠皮质神经元中，树突上很少有棘，Sema3A不会在树突上诱导PSD-95簇的形成。Sema3A及其受体基因在出生后10天和15天突触发生期间高度表达。sema3A缺失和fyn缺失小鼠的第五层皮质神经元树突上突触钮扣样结构密度降低，而第三层神经元密度没有变化。双杂合小鼠的神经元脊柱密度降低，而单杂合小鼠的神经元脊柱密度与野生型相近。这些发现提示Sema3A信号通路在大脑皮层神经元树突棘成熟的调控中起重要作用。
A member of semaphorin family, semaphorin3A (Sema3A), acts as a chemorepellent or chemoattractant on a wide variety of axons and dendrites in the development of the nervous systems. We here show that Sema3A induces clustering of both postsynaptic density-95 (PSD-95) and presynaptic synapsin I in cultured cortical neurons without changing the density of spines or filopodia. Neuropilin-1 (NRP-1), a receptor for Sema3A, is present on both axons and dendrites. When the cultured neurons are exposed to Sema3A, the cluster size of PSD-95 is markedly enhanced, and an extensive colocalization of PSD-95 and NRP-1 or actin-rich protrusion is seen. The effects of Sema3A on spine morphology are blocked by PP2, an Src type tyrosine kinase inhibitor, but not by the PP3, the inactive-related compound. In the cultured cortical neurons from fyn(-/-) mice, dendrites bear few spines, and Sema3A does not induce PSD-95 cluster formation on the dendrites. Sema3A and its receptor genes are highly expressed during the synaptogenic period of postnatal days 10 and 15. The cortical neurons in layer V, but not layer III, show a lowered density of synaptic bouton-like structure on dendrites in sema3A- and fyn-deficient mice. The neurons of the double-heterozygous mice show the lowered spine density, whereas those of single heterozygous mice show similar levels of the spine density as the wild type. These findings suggest that the Sema3A signaling pathway plays an important role in the regulation of dendritic spine maturation in the cerebral cortex neurons.