Bonanomi Dario, Menegon Andrea, Miccio Annarita, Ferrari Giuliana, Corradi Anna, Kao Hung-Teh, Benfenati Fabio, Valtorta Flavia
Department of Neuroscience, San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy.
J Neurosci. 2005 Aug 10;25(32):7299-308. doi: 10.1523/JNEUROSCI.1573-05.2005.
In developing neurons, synaptic vesicles (SVs) undergo cycles of exo-endocytosis along isolated axons. However, it is currently unknown whether SV exocytosis is regulated before synaptogenesis. Here, we show that cAMP-dependent pathways affect SV distribution and recycling in the axonal growth cone and that these effects are mediated by the SV-associated phosphoprotein synapsin I. The presence of synapsin I on SVs is necessary for the correct localization of the vesicles in the central portion of the growth cone. Phosphorylation of synapsin I by cAMP-dependent protein kinase (protein kinase A) causes the dissociation of the protein from the SV membrane, allowing diffusion of the vesicles to the periphery of the growth cone and enhancing their rate of recycling. These results provide new clues as to the bases of the well known activity of synapsin I in synapse maturation and indicate that molecular mechanisms similar to those operating at mature nerve terminals are active in developing neurons to regulate the SV life cycle before synaptogenesis.
在发育中的神经元中，突触小泡（SVs）沿着孤立的轴突进行胞吐 - 内吞循环。然而，目前尚不清楚突触小泡的胞吐作用在突触形成之前是否受到调控。在这里，我们表明cAMP依赖性途径影响轴突生长锥中突触小泡的分布和循环，并且这些作用是由与突触小泡相关的磷蛋白突触素I介导的。突触小泡上存在突触素I对于小泡在生长锥中央部分的正确定位是必要的。cAMP依赖性蛋白激酶（蛋白激酶A）对突触素I的磷酸化导致该蛋白从突触小泡膜上解离，使小泡扩散到生长锥的周边并提高其循环速率。这些结果为突触素I在突触成熟中众所周知的活性基础提供了新线索，并表明与在成熟神经末梢起作用的分子机制类似的机制在发育中的神经元中活跃，以在突触形成之前调节突触小泡的生命周期。
