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Science. 2017 Nov 3;358(6363):623-630. doi: 10.1126/science.aan6009.

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

Hirabayashi Y1,2,3,4, Kwon SK1,2,3, Paek H1,2,3, Pernice WM5, Paul MA1,2,3, Lee J1,2,3, Erfani P1,2,3, Raczkowski A6, Petrey DS7,8, Pon LA5,9, Polleux F10,2,3.

Author information

1
Department of Neuroscience, Columbia University Medical Center, Columbia University, New York, NY 10027, USA.
2
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
3
Kavli Institute for Brain Science, Columbia University, New York, NY 10027, USA.
4
Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan.
5
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
6
Simons Electron Microscopy Center, New York Structural Biology Center (NYSBC), New York, NY 10027, USA.
7
Center for Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, New York, NY 10032, USA.
8
Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
9
Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
10
Department of Neuroscience, Columbia University Medical Center, Columbia University, New York, NY 10027, USA. fp2304@cumc.columbia.edu.

Abstract

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.

Comment in

PMID:
29097544
PMCID:
PMC5818999
DOI:
10.1126/science.aan6009
[Indexed for MEDLINE]
Free PMC Article

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