The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes

Publication type:
Journal article
Metadata:
Autoren
  • Jacek Krzysko
  • Filip Maciag
  • Anna Mertens
  • Baran Enes Gueler
  • Joshua Linnert
  • Karsten Boldt
  • Marius Ueffing
  • Kerstin Nagel-Wolfrum
  • Martin Heine
  • Uwe Wolfrum
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000858139300001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3390/cells11182790
eISSN
2073-4409
Externe Identifier
  • Clarivate Analytics Document Solution ID: 4T5EC
  • PubMed Identifier: 36139365
Ausgabe der Veröffentlichung
18
Zeitschrift
CELLS
Schlüsselwörter
  • adhesion GPCR
  • mitochondria-associated ER membranes (MAM)
  • mitochondria-endoplasmic reticulum contact sites (MERCS)
  • Ca2+ transient at ER and mitochondria
  • Ca2+ homeostasis
Artikelnummer
ARTN 2790
Datum der Veröffentlichung
2022
Status
Published
Titel
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca<SUP>2+</SUP> Homeostasis at Mitochondria-Associated ER Membranes
Sub types
  • Article
Ausgabe der Zeitschrift
11

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>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.</jats:p>
Autoren
  • Jacek Krzysko
  • Filip Maciag
  • Anna Mertens
  • Baran Enes Güler
  • Joshua Linnert
  • Karsten Boldt
  • Marius Ueffing
  • Kerstin Nagel-Wolfrum
  • Martin Heine
  • Uwe Wolfrum
DOI
10.3390/cells11182790
eISSN
2073-4409
Ausgabe der Veröffentlichung
18
Zeitschrift
Cells
Sprache
en
Online publication date
2022
Paginierung
2790 - 2790
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/cells11182790
Datum der Datenerfassung
2022
Titel
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes
Ausgabe der Zeitschrift
11

Data source: Crossref

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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> homeostasis, one of the key functions of MAMs.
Addresses
  • Institute of Molecular Physiology (imP), Molecular Cell Biology, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Autoren
  • Jacek Krzysko
  • Filip Maciag
  • Anna Mertens
  • Baran Enes Güler
  • Joshua Linnert
  • Karsten Boldt
  • Marius Ueffing
  • Kerstin Nagel-Wolfrum
  • Martin Heine
  • Uwe Wolfrum
DOI
10.3390/cells11182790
eISSN
2073-4409
Externe Identifier
  • PubMed Identifier: 36139365
  • PubMed Central ID: PMC9496679
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: DFG FOR 2149, project number 246212759
  • Foundation Fighting Blindness: PPA-0717-0719-RAD
  • Deutsche Forschungsgemeinschaft: SPP SPP2127 - Gene and Cell based therapies to counteract neuroretinal degeneration, project numbers: 399443882
  • Leibniz Institute for Neurobiology: FM, MH
Open access
true
ISSN
2073-4409
Ausgabe der Veröffentlichung
18
Zeitschrift
Cells
Schlüsselwörter
  • Endoplasmic Reticulum
  • Mitochondria
  • Animals
  • Humans
  • Mice
  • Homeostasis
  • Child
  • Mitochondrial Membranes
Sprache
eng
Medium
Electronic
Online publication date
2022
Open access status
Open Access
Paginierung
2790
Datum der Veröffentlichung
2022
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2022
Titel
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca<sup>2+</sup> Homeostasis at Mitochondria-Associated ER Membranes.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
11

Files

https://www.mdpi.com/2073-4409/11/18/2790/pdf?version=1662544865 https://europepmc.org/articles/PMC9496679?pdf=render

Data source: Europe PubMed Central

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.
Date of acceptance
2022
Autoren
  • Jacek Krzysko
  • Filip Maciag
  • Anna Mertens
  • Baran Enes Güler
  • Joshua Linnert
  • Karsten Boldt
  • Marius Ueffing
  • Kerstin Nagel-Wolfrum
  • Martin Heine
  • Uwe Wolfrum
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36139365
DOI
10.3390/cells11182790
eISSN
2073-4409
Externe Identifier
  • PubMed Central ID: PMC9496679
Ausgabe der Veröffentlichung
18
Zeitschrift
Cells
Schlüsselwörter
  • Ca2+ homeostasis
  • Ca2+ transient at ER and mitochondria
  • adhesion GPCR
  • mitochondria-associated ER membranes (MAM)
  • mitochondria-endoplasmic reticulum contact sites (MERCS)
  • Animals
  • Child
  • Endoplasmic Reticulum
  • Homeostasis
  • Humans
  • Mice
  • Mitochondria
  • Mitochondrial Membranes
Sprache
eng
Country
Switzerland
PII
cells11182790
Datum der Veröffentlichung
2022
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
11

Data source: PubMed

Author's licence
CC-BY
Autoren
  • Jacek Krzysko
  • Filip Maciag
  • Anna Mertens
  • Baran Enes Güler
  • Joshua Linnert
  • Karsten Boldt
  • Marius Ueffing
  • Kerstin Nagel-Wolfrum
  • Martin Heine
  • Uwe Wolfrum
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3390/cells11182790
Funding acknowledgements
  • Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577
File(s) embargoed
false
Open access
true
ISSN
2073-4409
Zeitschrift
Cells
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Open access status
Open Access
Paginierung
18
Datum der Veröffentlichung
2022
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/8199
Herausgeber
MDPI
Datum der Datenerfassung
2022
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Zugang
Public
Titel
The adhesion GPCR VLGR1/ADGRV1 regulates the Ca2+ homeostasis at mitochondria-associated ER membranes
Ausgabe der Zeitschrift
11

Files

the_adhesion_gpcr_vlgr1adgrv1-20221026143936447.pdf

Data source: OPENSCIENCE.UB

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