Amato Stephen, Man Heng-Ye
Department of Biology; Boston University; Boston, MA USA.
Commun Integr Biol. 2012 Mar 1;5(2):152-5. doi: 10.4161/cib.18968.
Neuronal polarization, the process by which neurons form multiple dendrites and an axon from the soma, is the first critical step in the formation and function of neural networks. Polarization begins with the rapid extension of a single neurite to produce an axon of impressive size and complex geometry, while the remaining sister neurites differentiate into dendrites. The extensive biosynthesis required to produce an axon therefore necessitates coordination with cellular energy status to ensure an ample energy supply. Our recent work shows that activity of the AMP-activated protein kinase (AMPK), the bio-energy sensor responsible for maintaining cellular energy homeostasis in all eukaryotic cells, plays an important role in the initiation of axonal growth. AMPK phosphorylates the cargo-binding light chain of the Kif5 motor protein, leading to dissociation of the phosphatidylinositol 3-Kinase (PI3K) from the motor complex. The mislocation of PI3K, which is normally enriched at the axonal tip for extension and differentiation, results in a lack of neurite specification and neuron polarization. These findings reveal a link between cellular bioenergy homeostasis and neuron morphogenesis, and suggest a novel cellular mechanism underlying the long-term neurological abnormalities as a consequence of bioenergy deficiency during early brain development.
神经元极化是指神经元从胞体形成多个树突和一个轴突的过程，是神经网络形成和功能的首个关键步骤。极化始于单个神经突的快速延伸，以产生一个尺寸可观且几何形状复杂的轴突，而其余的姐妹神经突则分化为树突。因此，产生轴突所需的广泛生物合成需要与细胞能量状态相协调，以确保充足的能量供应。我们最近的研究表明，AMP激活的蛋白激酶（AMPK）的活性，即负责维持所有真核细胞中细胞能量稳态的生物能量传感器，在轴突生长的起始过程中起重要作用。AMPK使Kif5运动蛋白的货物结合轻链磷酸化，导致磷脂酰肌醇3激酶（PI3K）从运动复合体中解离。PI3K通常富集于轴突尖端以进行延伸和分化，其错位导致神经突特化和神经元极化缺失。这些发现揭示了细胞生物能量稳态与神经元形态发生之间的联系，并提示了一种新的细胞机制，该机制是早期脑发育过程中生物能量缺乏导致长期神经异常的基础。
