Akt/PKB Controls the Activity-Dependent Bulk Endocytosis of Synaptic Vesicles
Akt/PKB Controls the Activity-Dependent Bulk Endocytosis of Synaptic Vesicles
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Akt/PKB 控制突触小泡的活性依赖性大量内吞作用
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
M. Cousin
中科院分区：
文献类型：
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作者：
K. J. Smillie;M. Cousin
活动依赖性大体积内吞作用（ADBE）是SV在强烈神经元活动期间主要的内吞作用模式。动力蛋白I上Ser774的去磷酸化是触发ADBE的必要条件，随后糖原合成酶激酶3 （GSK3）对其进行再磷酸化也是如此。我们发现，在小脑颗粒神经元的原代培养中，蛋白激酶Akt在神经元强烈活动时磷酸化GSK3，确保GSK3在强烈刺激时失活，以帮助动力蛋白I去磷酸化。此外，当在原代神经元培养物中过表达一种构成活性形式的Akt时，ADBE被抑制，而对网格蛋白介导的内吞作用没有影响。因此，Akt有两个主要的调节作用：(1)通过对GSK3的急性活性依赖性抑制来确保有效的动力蛋白i去磷酸化；(2)在长期激活时负调控ADBE。这是Akt在SV循环中的作用的首次证明，并表明该蛋白激酶在神经元活动升高期间调节突触强度方面发挥关键作用。
Activity‐dependent bulk endocytosis (ADBE) is the dominant SV endocytosis mode during intense neuronal activity. The dephosphorylation of Ser774 on dynamin I is essential for triggering of ADBE, as is its subsequent rephosphorylation by glycogen synthase kinase 3 (GSK3). We show that in primary cultures of cerebellar granule neurons the protein kinase Akt phosphorylates GSK3 during intense neuronal activity, ensuring that GSK3 is inactive during intense stimulation to aid dynamin I dephosphorylation. Furthermore, when a constitutively active form of Akt was overexpressed in primary neuronal cultures, ADBE was inhibited with no effect on clathrin‐mediated endocytosis. Thus Akt has two major regulatory roles (i) to ensure efficient dynamin I dephosphorylation via acute activity‐dependent inhibition of GSK3 and (ii) to negatively regulate ADBE when activated in the longer term. This is the first demonstration of a role for Akt in SV recycling and suggests a key role for this protein kinase in modulating synaptic strength during elevated neuronal activity.
DOI：
10.1172/jci20016
发表时间：
2004-10
期刊：
The Journal of clinical investigation
影响因子：
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作者：
E. Bernal-Mizrachi;S. Fátrai;James D. Johnson;M. Ohsugi;K. Otani;Zhi-qiang Han;K. Polonsky;M. Permutt
通讯作者：
E. Bernal-Mizrachi;S. Fátrai;James D. Johnson;M. Ohsugi;K. Otani;Zhi-qiang Han;K. Polonsky;M. Permutt
影响因子：
3.3
作者：
Gonzalez, Eva;McGraw, Timothy E.
通讯作者：
McGraw, Timothy E.