Ligon Cheryl, Cai Yu, Buch Shilpa, Arikkath Jyothi
Developmental Neuroscience, Munroe-Meyer Institute, United States.
Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center, Omaha, NE, 68198, United States.
Neurosci Lett. 2020 Jun 21;730:135048. doi: 10.1016/j.neulet.2020.135048. Epub 2020 May 19.
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, both in vitro and in 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.
锥体神经元具有独特的形态，这对于它们融入功能性神经回路的能力至关重要。除了轴突-树突极性外，锥体神经元还表现出树突极性，使得顶端和基底外侧树突在大小、结构和输入方面存在差异。锥体神经元中的树突极性与高尔基体的极性一致，这是一个在体外和体内与定向分泌运输相关的关键特征。我们发现了一种基于自噬的新机制，该机制使高尔基体的极性与树突极性解偶联。自噬是一种普遍的细胞途径，通过降解细胞成分来促进细胞内稳态。我们的数据表明，自噬机制的关键成分ATG7的敲低会破坏高尔基体的极性，而不会影响原代锥体神经元中的树突极性，这提供了树突极性可以与高尔基体极性解偶联的首个证据。有趣的是，这些效应仅限于ATG7的敲低，自噬机制的另一个成分ATG16L1的敲低并不会产生同样的效果。我们提出存在将高尔基体极性与树突极性偶联的细胞机制。自噬机制的成分被用来积极地将高尔基体极性与树突极性偶联，从而影响锥体神经元中单个树突的分泌运输。
