Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking.
Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking.
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DOI：
10.1083/jcb.201912045
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
Casals N
中科院分区：
文献类型：
--
作者：
Casas M;Fadó R;Domínguez JL;Roig A;Kaku M;Chohnan S;Solé M;Unzeta M;Miñano-Molina AJ;Rodríguez-Álvarez J;Dickson EJ;Casals N
含GuA 1的AMPA受体在突触可塑性和认知中起关键作用。Casas等人证明，CPT 1C对营养物质的感知调节了SAC 1的磷酸酶活性，从而调节了内质网和高尔基体网络之间接触位点的PI（4）P水平，以控制GluA 1受体向神经元细胞表面的运输。肉毒碱棕榈酰转移酶1C（CPT 1C）是丙二酰辅酶A的传感器，位于神经元的内质网。AMPA受体（AMPAR）介导大脑中的快速兴奋性神经传递，并在突触可塑性中发挥关键作用。在本研究中，我们证明了在不同的代谢应激条件下，调节丙二酰辅酶A水平的皮质神经元，CPT 1C调节的主要AMPAR亚基，GluA 1，通过磷脂酰肌醇-4-磷酸（PI（4）P）磷酸酶SAC 1的贩运。在正常条件下，CPT 1C下调SAC 1催化活性，使有效的GluA 1运输到质膜。然而，在低丙二酰辅酶A水平下，例如在葡萄糖消耗期间，释放对SAC 1的CPT 1C依赖性抑制，促进SAC 1易位到ER-TGN接触位点，以减少TGN PI（4）P库并触发GluA 1在TGN的保留。结果表明，GluA 1的运输调节CPT 1C传感丙二酰辅酶A，并提供了第一个报告的SAC 1抑制剂。此外，他们揭示了营养物质如何影响突触功能和认知。
GuA1-containing AMPA receptors play a key role in synaptic plasticity and cognition. Casas et al. demonstrate that the sensing of nutrients by CPT1C regulates the phosphatase activity of SAC1, and consequently PI(4)P levels, at the contact sites between the endoplasmic reticulum and the trans-Golgi network to control the trafficking of GluA1 receptors to the cell surface of neurons. Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and is located in the ER of neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the brain and play a key role in synaptic plasticity. In the present study, we demonstrate across different metabolic stress conditions that modulate malonyl-CoA levels in cortical neurons that CPT1C regulates the trafficking of the major AMPAR subunit, GluA1, through the phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. In normal conditions, CPT1C down-regulates SAC1 catalytic activity, allowing efficient GluA1 trafficking to the plasma membrane. However, under low malonyl-CoA levels, such as during glucose depletion, CPT1C-dependent inhibition of SAC1 is released, facilitating SAC1’s translocation to ER-TGN contact sites to decrease TGN PI(4)P pools and trigger GluA1 retention at the TGN. Results reveal that GluA1 trafficking is regulated by CPT1C sensing of malonyl-CoA and provide the first report of a SAC1 inhibitor. Moreover, they shed light on how nutrients can affect synaptic function and cognition.
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DOI：
10.1523/jneurosci.1423-10.2010
发表时间：
2010-06-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dworak M;McCarley RW;Kim T;Kalinchuk AV;Basheer R
通讯作者：
Basheer R
影响因子：
4.8
作者：
Gratacòs-Batlle E;Olivella M;Sánchez-Fernández N;Yefimenko N;Miguez-Cabello F;Fadó R;Casals N;Gasull X;Ambrosio S;Soto D
通讯作者：
Soto D
DOI：
10.1007/978-1-61779-139-0_13
发表时间：
2011-01-01
期刊：
IMMUNE RECEPTORS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Bohdanowicz, Michel;Fairn, Gregory D.
通讯作者：
Fairn, Gregory D.
DOI：
10.1126/science.aab1370
发表时间：
2015-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
De Camilli P
影响因子：
4.4
作者：
Chen, Ning;Pandya, Nikhil J.;Li, Ka Wan
通讯作者：
Li, Ka Wan