ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
The glutamic acid-rich protein is a gating inhibitor of cyclic nucleotide-gated channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Alternative splicing governs cone cyclic nucleotide-gated (CNG) channel sensitivity to regulation by phosphoinositides.The Journal of biological chemistry · 2014Trial
- Selective knockout of murine glutamic acid-rich protein 2 significantly alters dark continuous noise in rod photoreceptors.The Journal of physiology · 2026Article
- CNG channel-related retinitis pigmentosa.Vision research · 2023Article
- Cellular and Molecular Mechanisms of Pathogenesis Underlying Inherited Retinal Dystrophies.Biomolecules · 2023Review
- Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.Biomedicines · 2023Review
- Structural mechanisms of assembly, permeation, gating, and pharmacology of native human rod CNG channel.Neuron · 2022Article
- CNGB1-related rod-cone dystrophy: A mutation review and update.Human mutation · 2021Review
- Variable expressivity in patients with autosomal recessive retinitis pigmentosa associated with the geneOphthalmic genetics · 2021Article
- Isolated rod dysfunction associated with a novel genotype ofAmerican journal of ophthalmology case reports · 2019Article
- Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.JAMA ophthalmology · 2018Article
- Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.International journal of molecular sciences · 2018Review
- GARP2 accelerates retinal degeneration in rod cGMP-gated cation channel β-subunit knockout mice.Scientific reports · 2017Article
- Molecular basis for photoreceptor outer segment architecture.Progress in retinal and eye research · 2016Review
- Role of RDS and Rhodopsin in Cngb1-Related Retinal Degeneration.Investigative ophthalmology & visual science · 2016Article
- AAV Vectors for FRET-Based Analysis of Protein-Protein Interactions in Photoreceptor Outer Segments.Frontiers in neuroscience · 2016Article
- Varying the GARP2-to-RDS Ratio Leads to Defects in Rim Formation and Rod and Cone Function.Investigative ophthalmology & visual science · 2015Article
- Protein and Signaling Networks in Vertebrate Photoreceptor Cells.Frontiers in molecular neuroscience · 2015Review
- Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina.Cell communication and signaling : CCS · 2014Article
- Gene replacement therapy for retinal CNG channelopathies.Molecular genetics and genomics : MGG · 2013Review
- CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide sensitivity of cone photoreceptor CNG channels by altering intersubunit interactions.American journal of physiology. Cell physiology · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic nucleotide-gated (CNG) cation channel of rod photoreceptors is a heterotetramer consisting of homologous CNGA1 and CNGB1a subunits. While CNGA1 is indispensable for channel activation, the specific role of CNGB1a in this process has remained elusive. Here, we show that the N-terminal glutamic acid-rich protein (GARP) domain of CNGB1a and soluble GARP2, which corresponds to the proximal portion of the GARP domain, act as autoinhibitory domains that decrease the opening probability of the CNG channel. In the presence of mutations that structurally impair the cyclic nucleotide-binding domain (CNBD) of CNGB1a, the GARP domain completely abolishes channel activity. In agreement with an inhibitory function of GARP, the activity of mutant CNG channels could be fully restored by deletion of the GARP domain. We identified two sequences within the GARP domain that confer most of the inhibitory effect and demonstrate that the profound inhibition imposed by the GARP domain is caused by direct and autonomous protein-protein interaction with the CNG channel complex. In wild-type rod CNG channels, this inhibitory effect can be relieved by binding of cGMP to the CNBD of CNGB1a. In conclusion, we propose that the N terminus of CNGB1a and soluble GARPs act as molecular gate keepers that control the activation of heteromeric rod CNG channels. Our results suggest that the GARP domain has evolved in rod photoreceptors to reduce current noise resulting from openings of CNG channels in the absence of cGMP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.