The Palmitoylation Machinery Is a Spatially Organizing System for Peripheral Membrane Proteins
The Palmitoylation Machinery Is a Spatially Organizing System for Peripheral Membrane Proteins
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DOI：
10.1016/j.cell.2010.04.007
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发表时间：
2010-04-30
期刊：
影响因子：
64.5
通讯作者：
Bastiaens, Philippe I. H.
中科院分区：
文献类型：
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作者：
Rocks, Oliver;Gerauer, Marc;Bastiaens, Philippe I. H.
半胱氨酸残基的可逆s -棕榈酰化关键控制外周膜蛋白的瞬态膜系泊。棕榈酰化机制如何控制它们的定位和功能尚不清楚。我们利用半合成底物监测了核心哺乳动物棕榈酰化机制的空间分解反应动力学和底物特异性。棕榈酰化仅在高尔基体上可检测到，而去棕榈酰化在细胞中无处不在。这些反应没有立体选择性，也缺乏基本的一致序列，这表明底物特异性对于去-/再棕榈酰化并不是必需的。棕榈酸酯的附着和去除都需要几秒钟才能完成。这种反应地形和快速动力学允许通过后高尔基分选装置连续重定向错误定位的蛋白质。单向分泌确保高尔基体和质膜之间的蛋白质分布保持适当的稳态，这与内体是连续的。这种通用的空间组织系统不同于传统的受体介导的靶向机制，并有效地抵消了棕榈酰化外周膜蛋白在所有膜上的熵驱动的再分配。
Reversible S-palmitoylation of cysteine residues critically controls transient membrane tethering of peripheral membrane proteins. Little is known about how the palmitoylation machinery governs their defined localization and function. We monitored the spatially resolved reaction dynamics and substrate specificity of the core mammalian palmitoylation machinery using semisynthetic substrates. Palmitoylation is detectable only on the Golgi, whereas depalmitoylation occurs everywhere in the cell. The reactions are not stereoselective and lack any primary consensus sequence, demonstrating that substrate specificity is not essential for de-/repalmitoylation. Both palmitate attachment and removal require seconds to accomplish. This reaction topography and rapid kinetics allows the continuous redirection of mislocalized proteins via the post-Golgi sorting apparatus. Unidirectional secretion ensures the maintenance of a proper steady-state protein distribution between the Golgi and the plasma membrane, which are continuous with endosomes. This generic spatially organizing system differs from conventional receptor-mediated targeting mechanisms and efficiently counteracts entropy-driven redistribution of palmitoylated peripheral membrane proteins over all membranes.