Munc18 and Munc13 regulate early neurite outgrowth.
Munc18 and Munc13 regulate early neurite outgrowth.
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DOI：
10.1042/bc20100036
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发表时间：
2010-06-30
影响因子：
2.7
通讯作者：
Verhage M
中科院分区：
文献类型：
--
作者：
Broeke JH;Roelandse M;Luteijn MJ;Boiko T;Matus A;Toonen RF;Verhage M
背景信息。在发育过程中，向外生长的神经元的生长锥表达参与囊泡分泌的蛋白质，例如 SNARE（可溶性 N-乙基马来酰亚胺敏感融合蛋白-附着蛋白受体）蛋白、Munc13 和 Munc18。已知囊泡在突触形成之前融合在生长锥中，这可能有助于生长。结果。我们在两只释放缺陷小鼠（Munc18-1 null 和 Munc13-1/2 double null）的分离细胞培养物和器官切片培养物中测试了这种可能性。两种类型的释放缺陷神经元的生长速度均降低，因此在早期发育过程中神经突总长度较小[DIV1-4（体外第 1-4 天）]。此外，在 Munc18-1 null 神经元中观察到每个生长锥有更多的丝状伪足，但在 WT（野生型）或 Munc13-1/2 双 null 神经元中没有观察到。突触发生后不再观察到早期发育期间较小的总神经突长度（DIV14-23）。结论。这些数据表明，生长锥中囊泡融合的无法在生长速度高的初始阶段影响生长，但在突触发生期间/之后不影响生长。总的来说，在神经元网络形成过程中，生长速度可能不是速率限制，至少在体外是这样。此外，Munc18（而非 Munc13）可能通过之前观察到的对丝状肌动蛋白的影响来调节生长锥丝状伪足。
Background information. During development, growth cones of outgrowing neurons express proteins involved in vesicular secretion, such as SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins, Munc13 and Munc18. Vesicles are known to fuse in growth cones prior to synapse formation, which may contribute to outgrowth. Results. We tested this possibility in dissociated cell cultures and organotypic slice cultures of two release-deficient mice (Munc18-1 null and Munc13-1/2 double null). Both types of release-deficient neurons have a decreased outgrowth speed and therefore have a smaller total neurite length during early development [DIV1–4 (day in vitro 1–4)]. In addition, more filopodia per growth cone were observed in Munc18-1 null, but not WT (wild-type) or Munc13-1/2 double null neurons. The smaller total neurite length during early development was no longer observed after synaptogenesis (DIV14–23). Conclusion. These data suggest that the inability of vesicle fusion in the growth cone affects outgrowth during the initial phases when outgrowth speed is high, but not during/after synaptogenesis. Overall, the outgrowth speed is probably not rate-limiting during neuronal network formation, at least in vitro. In addition, Munc18, but not Munc13, regulates growth cone filopodia, potentially via its previously observed effect on filamentous actin.