Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors

Autoren

HG Körschen
M Beyermann
F Müller
M Heck
M Vantler
KW Koch
R Kellner
U Wolfrum
C Bode
KP Hofmann
UB Kaupp

Autoren-URL

https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000082131100049&DestLinkType=FullRecord&DestApp=WOS_CPL

DOI

10.1038/23468

eISSN

1476-4687

Externe Identifier

Clarivate Analytics Document Solution ID: 228HM
PubMed Identifier: 10466724

ISSN

0028-0836

Ausgabe der Veröffentlichung

6746

Zeitschrift

NATURE

Paginierung

761 - 766

Datum der Veröffentlichung

1999

Status

Published

Titel

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors

Sub types

Article

Ausgabe der Zeitschrift

400

Data source: Web of Science (Lite)

Autoren

Heinz G Körschen
Michael Beyermann
Frank Müller
Martin Heck
Marius Vantler
Karl-Wilhelm Koch
Roland Kellner
Uwe Wolfrum
Christian Bode
Klaus Peter Hofmann
U Benjamin Kaupp

DOI

10.1038/23468

eISSN

1476-4687

ISSN

0028-0836

Ausgabe der Veröffentlichung

6746

Zeitschrift

Nature

Sprache

en

Paginierung

761 - 766

Datum der Veröffentlichung

1999

Status

Published

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1038/23468

Datum der Datenerfassung

2021

Titel

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors

Ausgabe der Zeitschrift

400

Data source: Crossref

Abstract

The assembly of signalling molecules into macromolecular complexes (transducisomes) provides specificity, sensitivity and speed in intracellular signalling pathways. Rod photoreceptors in the eye contain an unusual set of glutamic-acid-rich proteins (GARPs) of unknown function. GARPs exist as two soluble forms, GARP1 and GARP2, and as a large cytoplasmic domain (GARP' part) of the beta-subunit of the cyclic GMP-gated channel. Here we identify GARPs as multivalent proteins that interact with the key players of cGMP signalling, phosphodiesterase and guanylate cyclase, and with a retina-specific ATP-binding cassette transporter (ABCR), through four, short, repetitive sequences. In electron micrographs, GARPs are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. GARP2, the most abundant splice form, associates more strongly with light-activated than with inactive phosphodiesterase, and GARP2 potently inhibits phosphodiesterase activity. Thus, the GARPs organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes. Because there are no similar GARPs in cones, we propose that GARPs may prevent unnecessary cGMP turnover during daylight, when rods are held in saturation by the relatively high light levels.

Addresses

Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, Germany.

Autoren

HG Körschen
M Beyermann
F Müller
M Heck
M Vantler
KW Koch
R Kellner
U Wolfrum
C Bode
KP Hofmann
UB Kaupp

DOI

10.1038/23468

eISSN

1476-4687

Externe Identifier

PubMed Identifier: 10466724

Open access

false

ISSN

0028-0836

Ausgabe der Veröffentlichung

6746

Zeitschrift

Nature

Schlüsselwörter

Animals
Cattle
Transducin
Phosphoric Diester Hydrolases
Guanylate Cyclase
Glutamic Acid
Proteins
ATP-Binding Cassette Transporters
Eye Proteins
Nerve Tissue Proteins
Recombinant Proteins
Cyclic GMP
Phosphodiesterase Inhibitors
Signal Transduction
Amino Acid Sequence
Protein Binding
Molecular Sequence Data
Cyclic Nucleotide-Gated Cation Channels
Rod Cell Outer Segment
Retinal Rod Photoreceptor Cells
In Vitro Techniques

Sprache

eng

Medium

Print

Paginierung

761 - 766

Datum der Veröffentlichung

1999

Status

Published

Datum der Datenerfassung

1999

Titel

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

400

Data source: Europe PubMed Central

Abstract

The assembly of signalling molecules into macromolecular complexes (transducisomes) provides specificity, sensitivity and speed in intracellular signalling pathways. Rod photoreceptors in the eye contain an unusual set of glutamic-acid-rich proteins (GARPs) of unknown function. GARPs exist as two soluble forms, GARP1 and GARP2, and as a large cytoplasmic domain (GARP' part) of the beta-subunit of the cyclic GMP-gated channel. Here we identify GARPs as multivalent proteins that interact with the key players of cGMP signalling, phosphodiesterase and guanylate cyclase, and with a retina-specific ATP-binding cassette transporter (ABCR), through four, short, repetitive sequences. In electron micrographs, GARPs are restricted to the rim region and incisures of discs in close proximity to the guanylate cyclase and ABCR, whereas the phosphodiesterase is randomly distributed. GARP2, the most abundant splice form, associates more strongly with light-activated than with inactive phosphodiesterase, and GARP2 potently inhibits phosphodiesterase activity. Thus, the GARPs organize a dynamic protein complex near the disc rim that may control cGMP turnover and possibly other light-dependent processes. Because there are no similar GARPs in cones, we propose that GARPs may prevent unnecessary cGMP turnover during daylight, when rods are held in saturation by the relatively high light levels.

Autoren

HG Körschen
M Beyermann
F Müller
M Heck
M Vantler
KW Koch
R Kellner
U Wolfrum
C Bode
KP Hofmann
UB Kaupp

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/10466724

DOI

10.1038/23468

ISSN

0028-0836

Ausgabe der Veröffentlichung

6746

Zeitschrift

Nature

Schlüsselwörter

ATP-Binding Cassette Transporters
Amino Acid Sequence
Animals
Cattle
Cyclic GMP
Cyclic Nucleotide-Gated Cation Channels
Eye Proteins
Glutamic Acid
Guanylate Cyclase
In Vitro Techniques
Molecular Sequence Data
Nerve Tissue Proteins
Phosphodiesterase Inhibitors
Phosphoric Diester Hydrolases
Protein Binding
Proteins
Recombinant Proteins
Retinal Rod Photoreceptor Cells
Rod Cell Outer Segment
Signal Transduction
Transducin

Sprache

eng

Country

England

Paginierung

761 - 766

Datum der Veröffentlichung

1999

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

1999

Titel

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

400

Data source: PubMed

Interaction of glutamic-acid-rich proteins with the cGMP signalling pathway in rod photoreceptors

Tools