ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons

作者：Hirabayahi Yusuke; Kwon Seok Kyu; Paek Hunki; Pernice Wolfgang M; Paul Maela A; Lee Jnoh; Erfani Parsa; Raczkowski Ashleigh; Petrey Donald S; Pon Liza A; Polleux Franck^*

来源：Science, 2017, 358(6363): 623-629.

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 (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.

• 出版日期2017-11-3