Authors:	Krzysko, Jacek Maciag, Filip Mertens, Anna Güler, Baran Enes Linnert, Joshua Boldt, Karsten Ueffing, Marius Nagel-Wolfrum, Kerstin Heine, Martin Wolfrum, Uwe
Title:	The adhesion GPCR VLGR1/ADGRV1 regulates the Ca2+ homeostasis at mitochondria-associated ER membranes
Online publication date:	31-Oct-2022
Year of first publication:	2022
Language:	english
Abstract:	The very large G protein-coupled receptor (VLGR1, ADGRV1) is the largest member of the adhesion GPCR family. Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well as childhood absence epilepsy. VLGR1 was previously found as membrane–membrane adhesion complexes and focal adhesions. Affinity proteomics revealed that in the interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment at the contact sites of both organelles. We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation assays in cells. Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point to an essential role of VLGR1 in the regulation of Ca2+ homeostasis, one of the key functions of MAMs.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8184
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Cells 11
Pages or article number:	18
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2022
ISSN:	2073-4409
Publisher DOI:	10.3390/cells11182790
Appears in collections:	DFG-491381577-G