Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling
Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling
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DOI：
10.3389/fncir.2013.00202
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发表时间：
2013-12-20
影响因子：
3.5
通讯作者：
Yamamoto, Nobuhiko
中科院分区：
文献类型：
--
作者：
Granseth, Bjorn;Fukushima, Yuichi;Yamamoto, Nobuhiko
在发育过程中，轴突对细胞外分子做出反应，形成分支。人们对其潜在的分子机制知之甚少。在这里，我们研究了神经营养素诱导的轴突分支与丘脑皮质轴突的突触小泡循环之间的关系。外源性应用脑源性神经营养因子(BDNF)显著增加丘脑皮质共培养中轴突的分支，而去除内源性BDNF则减少分支。过表达的AP180的C末端片段，可抑制网状蛋白介导的内吞作用，影响了细胞层的分布和分支点的数量。一个显性负突触素突变体，选择性地以突触小泡循环为靶点，强烈抑制轴突分支。此外，表达突变型突触素的轴突对脑源性神经营养因子的分枝促进作用具有抵抗力。这些结果提示，突触小泡的循环可能调节BDNF在轴突发育过程中的分支。
During development, axons form branches in response to extracellular molecules. Little is known about the underlying molecular mechanisms. Here, we investigate how neurotrophin-induced axon branching is related to synaptic vesicle cycling for thalamocortical axons. The exogenous application of brain-derived neurotrophic factor (BDNF) markedly increased axon branching in thalamocortical co-cultures, while removal of endogenous BDNF reduced branching. Over-expression of a C-terminal fragment of AP180 that inhibits clathrin-mediated endocytosis affected the laminar distribution and the number of branch points. A dominant-negative synaptotagmin mutant that selectively targets synaptic vesicle cycling, strongly suppressed axon branching. Moreover, axons expressing the mutant synaptotagmin were resistant to the branch-promoting effect of BDNF. These results suggest that synaptic vesicle cycling might regulate BDNF induced branching during the development of the axonal arbor.