AMP 激活的蛋白激酶通过干扰 PI 3-激酶的定位来调节神经元极化。
AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization.
机构信息
Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
出版信息
Science. 2011 Apr 8;332(6026):247-51. doi: 10.1126/science.1201678. Epub 2011 Mar 24.
Abstract
Axon-dendrite polarization is crucial for neural network wiring and information processing in the brain. Polarization begins with the transformation of a single neurite into an axon and its subsequent rapid extension, which requires coordination of cellular energy status to allow for transport of building materials to support axon growth. We found that activation of the energy-sensing adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway suppressed axon initiation and neuronal polarization. Phosphorylation of the kinesin light chain of the Kif5 motor protein by AMPK disrupted the association of the motor with phosphatidylinositol 3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting polarization and axon growth.
摘要
轴突-树突极化对于大脑神经网络的布线和信息处理至关重要。极化始于单个神经突转化为轴突及其随后的快速延伸，这需要协调细胞能量状态，以允许运输建筑材料来支持轴突生长。我们发现，激活能量感应腺苷 5'-单磷酸（AMP）激活蛋白激酶（AMPK）途径会抑制轴突起始和神经元极化。AMPK 对驱动蛋白 Kif5 的轻链的磷酸化会破坏马达与磷酸肌醇 3-激酶（PI3K）的结合，阻止 PI3K 靶向轴突尖端，并抑制极化和轴突生长。
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