Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Elvir Becirovic
- ON Phuong Nguyen
- Christos Paparizos
- Elisabeth S Butz
- Gabi Stern-Schneider
- Uwe Wolfrum
- Stefanie M Hauck
- Marius Ueffing
- Christian Wahl-Schott
- Stylianos Michalakis
- Martin Biel
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000344671900012&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1093/hmg/ddu323
- eISSN
- 1460-2083
- Externe Identifier
- Clarivate Analytics Document Solution ID: AT1CY
- PubMed Identifier: 24963162
- ISSN
- 0964-6906
- Ausgabe der Veröffentlichung
- 22
- Zeitschrift
- HUMAN MOLECULAR GENETICS
- Paginierung
- 5989 - 5997
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Titel
- Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors
- Sub types
- Article
- Ausgabe der Zeitschrift
- 23
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Elvir Becirovic
- ON Phuong Nguyen
- Christos Paparizos
- Elisabeth S Butz
- Gabi Stern-Schneider
- Uwe Wolfrum
- Stefanie M Hauck
- Marius Ueffing
- Christian Wahl-Schott
- Stylianos Michalakis
- Martin Biel
- DOI
- 10.1093/hmg/ddu323
- eISSN
- 1460-2083
- ISSN
- 0964-6906
- Ausgabe der Veröffentlichung
- 22
- Zeitschrift
- Human Molecular Genetics
- Sprache
- en
- Online publication date
- 2014
- Paginierung
- 5989 - 5997
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Herausgeber
- Oxford University Press (OUP)
- Herausgeber URL
- http://dx.doi.org/10.1093/hmg/ddu323
- Datum der Datenerfassung
- 2022
- Titel
- Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors
- Ausgabe der Zeitschrift
- 23
Datenquelle: Crossref
- Abstract
- Outer segments (OSs) of rod photoreceptors are cellular compartments specialized in the conversion of light into electrical signals. This process relies on the light-triggered change in the intracellular levels of cyclic guanosine monophosphate, which in turn controls the activity of cyclic nucleotide-gated (CNG) channels in the rod OS plasma membrane. The rod CNG channel is a macromolecular complex that in its core harbors the ion-conducting CNGA1 and CNGB1a subunits. To identify additional proteins of the complex that interact with the CNGB1a core subunit, we applied affinity purification of mouse retinal proteins followed by mass spectrometry. In combination with in vitro and in vivo co-immunoprecipitation and fluorescence resonance energy transfer (FRET), we found that the tetraspanin peripherin-2 links CNGB1a to the light-detector rhodopsin. Using immunoelectron microscopy, we found that this peripherin-2/rhodopsin/CNG channel complex localizes to the contact region between the disk rims and the plasma membrane. FRET measurements revealed that the fourth transmembrane domain (TM4) of peripherin-2 is required for the interaction with rhodopsin. Quantitatively, the binding affinity of the peripherin-2/rhodopsin interaction was in a similar range as that observed for rhodopsin dimers. Finally, we demonstrate that the p.G266D retinitis pigmentosa mutation found within TM4 selectively abolishes the binding of peripherin-2 to rhodopsin. This finding suggests that the specific disruption of the rhodopsin/peripherin-2 interaction in the p.G266D mutant might contribute to the pathophysiology in affected persons.
- Addresses
- Munich Center for Integrated Protein Science CIPSM and Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, München, Germany.
- Autoren
- Elvir Becirovic
- ON Phuong Nguyen
- Christos Paparizos
- Elisabeth S Butz
- Gabi Stern-Schneider
- Uwe Wolfrum
- Stefanie M Hauck
- Marius Ueffing
- Christian Wahl-Schott
- Stylianos Michalakis
- Martin Biel
- DOI
- 10.1093/hmg/ddu323
- eISSN
- 1460-2083
- Externe Identifier
- PubMed Identifier: 24963162
- Open access
- false
- ISSN
- 0964-6906
- Ausgabe der Veröffentlichung
- 22
- Zeitschrift
- Human molecular genetics
- Schlüsselwörter
- Retina
- Animals
- Humans
- Mice
- Retinitis Pigmentosa
- Rhodopsin
- Nerve Tissue Proteins
- Protein Structure, Tertiary
- Protein Binding
- Cyclic Nucleotide-Gated Cation Channels
- Retinal Rod Photoreceptor Cells
- Retinal Photoreceptor Cell Outer Segment
- Peripherins
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2014
- Paginierung
- 5989 - 5997
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Datum der Datenerfassung
- 2014
- Titel
- Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 23
Datenquelle: Europe PubMed Central
- Abstract
- Outer segments (OSs) of rod photoreceptors are cellular compartments specialized in the conversion of light into electrical signals. This process relies on the light-triggered change in the intracellular levels of cyclic guanosine monophosphate, which in turn controls the activity of cyclic nucleotide-gated (CNG) channels in the rod OS plasma membrane. The rod CNG channel is a macromolecular complex that in its core harbors the ion-conducting CNGA1 and CNGB1a subunits. To identify additional proteins of the complex that interact with the CNGB1a core subunit, we applied affinity purification of mouse retinal proteins followed by mass spectrometry. In combination with in vitro and in vivo co-immunoprecipitation and fluorescence resonance energy transfer (FRET), we found that the tetraspanin peripherin-2 links CNGB1a to the light-detector rhodopsin. Using immunoelectron microscopy, we found that this peripherin-2/rhodopsin/CNG channel complex localizes to the contact region between the disk rims and the plasma membrane. FRET measurements revealed that the fourth transmembrane domain (TM4) of peripherin-2 is required for the interaction with rhodopsin. Quantitatively, the binding affinity of the peripherin-2/rhodopsin interaction was in a similar range as that observed for rhodopsin dimers. Finally, we demonstrate that the p.G266D retinitis pigmentosa mutation found within TM4 selectively abolishes the binding of peripherin-2 to rhodopsin. This finding suggests that the specific disruption of the rhodopsin/peripherin-2 interaction in the p.G266D mutant might contribute to the pathophysiology in affected persons.
- Autoren
- Elvir Becirovic
- ON Phuong Nguyen
- Christos Paparizos
- Elisabeth S Butz
- Gabi Stern-Schneider
- Uwe Wolfrum
- Stefanie M Hauck
- Marius Ueffing
- Christian Wahl-Schott
- Stylianos Michalakis
- Martin Biel
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/24963162
- DOI
- 10.1093/hmg/ddu323
- eISSN
- 1460-2083
- Ausgabe der Veröffentlichung
- 22
- Zeitschrift
- Hum Mol Genet
- Schlüsselwörter
- Animals
- Cyclic Nucleotide-Gated Cation Channels
- Humans
- Mice
- Nerve Tissue Proteins
- Peripherins
- Protein Binding
- Protein Structure, Tertiary
- Retina
- Retinal Photoreceptor Cell Outer Segment
- Retinal Rod Photoreceptor Cells
- Retinitis Pigmentosa
- Rhodopsin
- Sprache
- eng
- Country
- England
- Paginierung
- 5989 - 5997
- PII
- ddu323
- Datum der Veröffentlichung
- 2014
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 23
Datenquelle: PubMed
- Beziehungen:
- Eigentum von