A selective role for a component of the autophagy pathway in coupling the Golgi apparatus to dendrite polarity in pyramidal neurons
A selective role for a component of the autophagy pathway in coupling the Golgi apparatus to dendrite polarity in pyramidal neurons
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DOI：
10.1016/j.neulet.2020.135048
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发表时间：
2020-05
影响因子：
2.5
通讯作者：
Cheryl Ligon;Yu Cai;S. Buch;J. Arikkath
中科院分区：
文献类型：
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作者：
Cheryl Ligon;Yu Cai;S. Buch;J. Arikkath
锥体神经元具有特征性形态，这对于它们整合到功能性神经回路中的能力至关重要。除了轴突树突极性之外，锥体神经元还表现出树突极性，使得顶侧树突和基底侧树突在大小、结构和输入上不同。锥体神经元的树突极性与高尔基体的极性一致，这是与体外和体内定向分泌运输相关的关键特征。我们确定了一种新的自噬机制，从树突极性的高尔基体的极性解耦。自噬是一种通过降解细胞成分来促进细胞内稳态的普遍细胞途径。我们的数据表明，自噬机制的一个关键组成部分，ATG7的敲低，破坏了高尔基体的极性，而不影响树突极性在初级锥体神经元，提供了第一个证据，树突极性可以从高尔基体极性解偶联。有趣的是，这些作用仅限于ATG7敲低，并且不能通过自噬机制的另一个组成部分ATG16L1的敲低来复制。我们提出，细胞机制存在耦合高尔基体极性树突极性。利用自噬机制的组分来主动地将高尔基体极性与树突极性偶联，从而影响分泌运输到锥体神经元中的单个树突中。
Pyramidal neurons have a characteristic morphology that is critical to their ability to integrate into functional neural circuits. In addition to axon dendrite polarity, pyramidal neurons also exhibit dendritic polarity such that apical and basolateral dendrites differ in size, structure and inputs. Dendrite polarity in pyramidal neurons coincides with polarity of the Golgi apparatus, a key feature relevant to directed secretory trafficking, bothin vitroandin vivo. We identify a novel autophagy based mechanism that uncouples the polarity of the Golgi apparatus from dendrite polarity. Autophagy is a universal cellular pathway that promotes cellular homeostasis via degradation of cellular components. Our data indicate that knockdown of ATG7, a key component of the autophagy mechanism, disrupts the polarity of the Golgi apparatus without impacting dendritic polarity in primary pyramidal neurons, providing the first evidence that dendrite polarity can be uncoupled from Golgi polarity. Interestingly, these effects are restricted to ATG7 knockdown and are not replicated by the knockdown of ATG16L1, another component of the autophagy mechanism. We propose that cellular mechanisms exist to couple Golgi polarity to dendrite polarity. Components of the autophagy mechanism are leveraged to actively couple Golgi polarity to dendrite polarity, thus impacting secretory trafficking into individual dendrites in pyramidal neurons.