论文标题 / ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons
期刊 / Science
发表时间 / 2017-11-03
数字识别码 / 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 (Ca2+) uptake by mitochondria after synaptically induced Ca2+-release from ER and thereby regulated cytoplasmic Ca2+ 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 Ca2+ dynamics in mammalian neurons.
（导读 严冰）在酵母中的 ERMES 复合物可连接内质网（ER）与线粒体，但后生动物中并未发现任何 ERMES 蛋白的直系同源物。本文报导，哺乳动物的 ER-线粒体连接形成需要 PDZD8 蛋白，其 SMP 域与酵母 Mmm1 的 SMP 域功能上同源。在神经细胞中，突触信号诱导 ER 释放 Ca2+ 后，需要 PDZD8 来实现线粒体的 Ca2+ 吸收，因此 ER-线粒体耦合很可能与神经细胞树突的 Ca2+ 动态变化有关。