Autoren:	Krzysko, Jacek Maciag, Filip Mertens, Anna Güler, Baran Enes Linnert, Joshua Boldt, Karsten Ueffing, Marius Nagel-Wolfrum, Kerstin Heine, Martin Wolfrum, Uwe
Titel:	The adhesion GPCR VLGR1/ADGRV1 regulates the Ca2+ homeostasis at mitochondria-associated ER membranes
Online-Publikationsdatum:	31-Okt-2022
Erscheinungsdatum:	2022
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	570 Biowissenschaften 570 Life sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 10 Biologie
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8184
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Cells 11
Seitenzahl oder Artikelnummer:	18
Verlag:	MDPI
Verlagsort:	Basel
Erscheinungsdatum:	2022
ISSN:	2073-4409
DOI der Originalveröffentlichung:	10.3390/cells11182790
Enthalten in den Sammlungen:	DFG-491381577-G