BDNF/trkB Induction of Calcium Transients through Ca(v)2.2 Calcium Channels in Motoneurons Corresponds to F-actin Assembly and Growth Cone Formation on β2-Chain Laminin (221).
BDNF/trkB Induction of Calcium Transients through Ca(v)2.2 Calcium Channels in Motoneurons Corresponds to F-actin Assembly and Growth Cone Formation on β2-Chain Laminin (221).
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DOI：
10.3389/fnmol.2017.00346
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发表时间：
2017
影响因子：
4.8
通讯作者：
Jablonka S
中科院分区：
文献类型：
--
作者：
Dombert B;Balk S;Lüningschrör P;Moradi M;Sivadasan R;Saal-Bauernschubert L;Jablonka S
初级运动神经元的自发Ca2+瞬态和肌动蛋白动力学与细胞分化（如轴突伸长和生长锥形成）相对应。脑源性神经营养因子（BDNF）及其受体trkB支持运动神经元存活和突触分化。然而，在运动神经元中，BDNF/trkB信号对自发Ca2+内流和轴突生长锥肌动蛋白动力学的影响尚未完全揭示。在我们的研究中，我们解决了神经营养因子信号如何与细胞自主兴奋性和生长锥形成相对应的问题。来自小鼠胚胎的初级运动神经元在突触特异性，含有层粘连蛋白的β2链异构体（221）上培养，通过自发Ca2+瞬态调节轴突伸长，而自发Ca2+瞬态又由轴突生长锥中n型特异性电压门控Ca2+通道（Cav2.2）的增强聚集诱导。trkB缺陷（trkBTK−/−）小鼠运动神经元不表达全长trkB受体和野生型运动神经元不含BDNF培养表现出自发Ca2+瞬态减少，这与轴突伸长改变和生长锥形态缺陷相对应，并伴有局部肌动蛋白细胞骨架的变化。反之，急性应用BDNF导致运动生长锥中自发Ca2+瞬态和Cav2.2聚集，以及trkB下游信号级联的激活，通过LIM激酶途径促进β-actin的稳定和profilin在Tyr129的磷酸化。最后，我们在laminin-221/211培养的胚胎运动神经元轴突生长锥中发现了神经元兴奋性和肌动蛋白动力学的相互调节。兴奋性受损导致轴突延伸和局部肌动蛋白细胞骨架失调，而β-肌动蛋白敲低则影响Cav2.2聚类。我们从我们的数据中得出结论，在胚胎运动神经元中，BDNF/trkB信号通过局部肌动蛋白细胞骨架的变化，伴随着Cav2.2聚集和局部钙瞬态的增加，促进轴突伸长和生长锥的形成。这些发现可能有助于探索在胚胎运动神经元成熟过程中可能失调导致运动神经元疾病的细胞机制。
Spontaneous Ca2+ transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca2+ influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation. Primary motoneurons from mouse embryos were cultured on the synapse specific, β2-chain containing laminin isoform (221) regulating axon elongation through spontaneous Ca2+ transients that are in turn induced by enhanced clustering of N-type specific voltage-gated Ca2+ channels (Cav2.2) in axonal growth cones. TrkB-deficient (trkBTK−/−) mouse motoneurons which express no full-length trkB receptor and wildtype motoneurons cultured without BDNF exhibited reduced spontaneous Ca2+ transients that corresponded to altered axon elongation and defects in growth cone morphology which was accompanied by changes in the local actin cytoskeleton. Vice versa, the acute application of BDNF resulted in the induction of spontaneous Ca2+ transients and Cav2.2 clustering in motor growth cones, as well as the activation of trkB downstream signaling cascades which promoted the stabilization of β-actin via the LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we identified a mutual regulation of neuronal excitability and actin dynamics in axonal growth cones of embryonic motoneurons cultured on laminin-221/211. Impaired excitability resulted in dysregulated axon extension and local actin cytoskeleton, whereas upon β-actin knockdown Cav2.2 clustering was affected. We conclude from our data that in embryonic motoneurons BDNF/trkB signaling contributes to axon elongation and growth cone formation through changes in the local actin cytoskeleton accompanied by increased Cav2.2 clustering and local calcium transients. These findings may help to explore cellular mechanisms which might be dysregulated during maturation of embryonic motoneurons leading to motoneuron disease.
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DOI：
10.1083/jcb.150.6.1423
发表时间：
2000-09-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Du J;Feng L;Yang F;Lu B
通讯作者：
Lu B
影响因子：
3.5
作者：
Ackermann, Bastian;Kroeber, Sandra;Wirth, Brunhilde
通讯作者：
Wirth, Brunhilde
DOI：
10.1083/jcb.200208001
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bommel H;Xie G;Rossoll W;Wiese S;Jablonka S;Boehm T;Sendtner M
通讯作者：
Sendtner M
影响因子：
25
作者：
Fletcher EV;Simon CM;Pagiazitis JG;Chalif JI;Vukojicic A;Drobac E;Wang X;Mentis GZ
通讯作者：
Mentis GZ
影响因子：
4
作者：
Del Poggetto, Edoardo;Bemporad, Francesco;Chiti, Fabrizio
通讯作者：
Chiti, Fabrizio