IMPAIRED NEURITE OUTGROWTH OF SRC-MINUS CEREBELLAR NEURONS ON THE CELL-ADHESION MOLECULE L1

IMPAIRED NEURITE OUTGROWTH OF SRC-MINUS CEREBELLAR NEURONS ON THE CELL-ADHESION MOLECULE L1
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DOI:
10.1016/0896-6273(94)90339-5
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发表时间:
1994-04-01
期刊:
影响因子:
16.2
通讯作者:
MANESS, PF
MANESS, PF
中科院分区:
医学1区
文献类型:
--
作者:
IGNELZI, MA;MILLER, DR;MANESS, PF

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非受体酪氨酸蛋白激酶pp60(c-src)、p59(Fyn)和pp62(c-yes)定位于发育中神经元的生长锥体,但其功能尚不明确。为了确定这些酪氨酸激酶是否能够调节底物依赖的轴突生长,分析了来自野生型、src(-)、fyn(-)和yes(-)小鼠的小脑神经元培养物在神经细胞黏附分子L1或细胞外基质蛋白层粘连蛋白上的突起生长。Src(-)神经元的L1突起伸长率降低,而fyn(-)或yes(-)神经元的突起伸长率无明显变化。在src(-)、fyn(-)或yes(-)神经元中,层粘连蛋白上的轴突延伸没有改变,这表明pp60(c-src)、p59(Fyn)或pp62(c-yes)不太可能参与整合素依赖的轴突生长。这些结果表明pp60(c-src)是L1介导的轴突生长中细胞内信号通路的一个组成部分,并提示与src相关的非受体酪氨酸激酶在神经系统中可能具有独特的、非冗余的功能。
The nonreceptor tyrosine protein kinases pp60(c-src), p59(fyn), and pp62(c-yes) are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src(-), fyn(-), and yes(-) mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src(-), but not in fyn(-) or yes(-) neurons. Neurite extension on laminin was unaltered in src(-), fyn(-), or yes(-) neurons, indicating that pp60(c-src), p59(fyn), or pp62(c-yes) is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60(c-src) is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.