Robles Estuardo, Huttenlocher Anna, Gomez Timothy M
Department of Anatomy, University of Wisconsin, Madison, WI 53713, USA.
Neuron. 2003 May 22;38(4):597-609. doi: 10.1016/s0896-6273(03)00260-5.
Spontaneous intracellular calcium (Ca2+) transients in growth cone filopodia reduce filopodial motility, slow neurite outgrowth, and promote turning when generated asymmetrically; however, the downstream effectors of these Ca2+ -dependent behaviors are unknown. We report that Ca2+ transients in filopodia activate the intracellular protease calpain, which slows neurite outgrowth and promotes repulsive growth cone turning upon local activation. Active calpain alters the balance between tyrosine kinase and phosphatase activities in filopodia, resulting in a net decrease in tyrosine phosphorylation, which mediates both filopodial stabilization and reduced lamellipodial protrusion. Our findings indicate that locally generated Ca2+ signals repel axon outgrowth through calpain-dependent regulation of phosphotyrosine signaling at integrin-mediated adhesion sites.
生长锥丝状伪足中的自发细胞内钙（Ca2+）瞬变会降低丝状伪足的运动性，减缓神经突生长，并在不对称产生时促进转向；然而，这些钙依赖性行为的下游效应器尚不清楚。我们报告称，丝状伪足中的钙瞬变会激活细胞内蛋白酶钙蛋白酶，该酶会减缓神经突生长，并在局部激活时促进生长锥排斥性转向。活性钙蛋白酶改变了丝状伪足中酪氨酸激酶和磷酸酶活性之间的平衡，导致酪氨酸磷酸化净减少，这介导了丝状伪足的稳定和片状伪足突出的减少。我们的研究结果表明，局部产生的钙信号通过钙蛋白酶对整合素介导的粘附位点处磷酸酪氨酸信号的依赖性调节来排斥轴突生长。
