由PDZD8介导的内质网-线粒体连接调控哺乳动物神经元中的钙动态。
ER-mitochondria tethering by PDZD8 regulates Ca dynamics in mammalian neurons.
作者信息
Hirabayashi Yusuke, Kwon Seok-Kyu, Paek Hunki, Pernice Wolfgang M, Paul Maëla A, Lee Jinoh, Erfani Parsa, Raczkowski Ashleigh, Petrey Donald S, Pon Liza A, Polleux Franck
机构信息
Department of Neuroscience, Columbia University Medical Center, Columbia University, New York, NY 10027, USA.
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
出版信息
Science. 2017 Nov 3;358(6363):623-630. doi: 10.1126/science.aan6009.
Interfaces between organelles are emerging as critical platforms for many biological responses in eukaryotic cells. In yeast, the ERMES complex is an endoplasmic reticulum (ER)-mitochondria tether composed of four proteins, three of which contain a SMP (synaptotagmin-like mitochondrial-lipid binding protein) domain. No functional ortholog for any ERMES protein has been identified in metazoans. Here, we identified PDZD8 as an ER protein present at ER-mitochondria contacts. The SMP domain of PDZD8 is functionally orthologous to the SMP domain found in yeast Mmm1. PDZD8 was necessary for the formation of ER-mitochondria contacts in mammalian cells. In neurons, PDZD8 was required for calcium ion (Ca) uptake by mitochondria after synaptically induced Ca-release from ER and thereby regulated cytoplasmic Ca dynamics. Thus, PDZD8 represents a critical ER-mitochondria tethering protein in metazoans. We suggest that ER-mitochondria coupling is involved in the regulation of dendritic Ca dynamics in mammalian neurons.
细胞器之间的界面正逐渐成为真核细胞中许多生物学反应的关键平台。在酵母中，ERMES复合物是一种由四种蛋白质组成的内质网（ER）-线粒体连接体，其中三种蛋白质含有SMP（类突触结合蛋白样线粒体-脂质结合蛋白）结构域。在后生动物中尚未鉴定出任何ERMES蛋白的功能直系同源物。在这里，我们鉴定出PDZD8是一种存在于ER-线粒体接触部位的内质网蛋白。PDZD8的SMP结构域在功能上与酵母Mmm1中的SMP结构域直系同源。PDZD8是哺乳动物细胞中ER-线粒体接触形成所必需的。在神经元中，突触诱导内质网释放钙离子（Ca）后，线粒体摄取Ca需要PDZD8，从而调节细胞质Ca动态。因此，PDZD8代表后生动物中一种关键的ER-线粒体连接蛋白。我们认为ER-线粒体偶联参与了哺乳动物神经元树突状Ca动态的调节。
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