Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95.
Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95.
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DOI：
10.1083/jcb.200903101
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发表时间：
2009-07-13
期刊：
影响因子：
--
通讯作者：
Fukata M
中科院分区：
文献类型：
--
作者：
Noritake J;Fukata Y;Iwanaga T;Hosomi N;Tsutsumi R;Matsuda N;Tani H;Iwanari H;Mochizuki Y;Kodama T;Matsuura Y;Bredt DS;Hamakubo T;Fukata M
蛋白质棕榈酰化是最常见的翻译后脂质修饰；其可逆性介导细胞内区室之间的蛋白质穿梭。 DHHC (Asp-His-His-Cys) 蛋白大家族已作为蛋白棕榈酰酰基转移酶 (PAT) 出现。然而，在生理背景下调节这些 PAT 的机制仍然未知。在本研究中，我们有效监测了突触支架 PSD-95 上的动态棕榈酸循环。我们发现阻断突触活性会快速诱导 PSD-95 棕榈酰化并介导 PSD-95 和相关 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）型谷氨酸受体的突触聚类。树突状定位的 DHHC2 而不是高尔基体驻留的 DHHC3 介导这种活性敏感的棕榈酰化。活性阻断后，DHHC2 易位至突触后密度以转导这种效应。这些数据表明，各个 DHHC 成员受到差异性调节，并且蛋白质棕榈酰化机制的动态募集能够响应细胞外信号对蛋白质运输进行分区调节。
Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a physiological context remain unknown. In this study, we efficiently monitored the dynamic palmitate cycling on synaptic scaffold PSD-95. We found that blocking synaptic activity rapidly induces PSD-95 palmitoylation and mediates synaptic clustering of PSD-95 and associated AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors. A dendritically localized DHHC2 but not the Golgi-resident DHHC3 mediates this activity-sensitive palmitoylation. Upon activity blockade, DHHC2 translocates to the postsynaptic density to transduce this effect. These data demonstrate that individual DHHC members are differentially regulated and that dynamic recruitment of protein palmitoylation machinery enables compartmentalized regulation of protein trafficking in response to extracellular signals.
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DOI：
10.1523/jneurosci.1042-04.2004
发表时间：
2004-06-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ashby MC;De La Rue SA;Ralph GS;Uney J;Collingridge GL;Henley JM
通讯作者：
Henley JM
影响因子：
4
作者：
Linder, ME;Deschenes, RJ
通讯作者：
Deschenes, RJ
影响因子：
4.8
作者：
Lobo, S;Greentree, WK;Deschenes, RJ
通讯作者：
Deschenes, RJ
影响因子：
16.2
作者：
Elias, Guillermo M.;Funke, Lars;Nicoll, Roger A.
通讯作者：
Nicoll, Roger A.
影响因子：
4.8
作者：
Fukata, Yuko;Iwanaga, Tsuyoshi;Fukata, Masaki
通讯作者：
Fukata, Masaki