Overexpression of rod photoreceptor glutamic acid rich protein 2 (GARP2) increases gain and slows recovery in mouse retina

Cell Communication and Signaling

Research

Jeffrey Messinger¹  Timothy W Kraft²  Alex S McKeown²  Shanta Sarfare³  Steven J Pittler⁴  Hongjun Wei⁵  Glen Rubin⁶ 

[1] Department of Ophthalmology, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Department of Vision Sciences, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Department of Vision Sciences, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Current address: Department of Ophthalmology, College of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA;Department of Vision Sciences, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Department of Ophthalmology, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Department of Vision Sciences, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Department of Pathology, Division of Molecular and Cellular Pathology, 35294, Birmingham, AL, USA;Department of Vision Sciences, University of Alabama at Birmingham, 35294-0019, Birmingham, AL, USA;Impulse Monitoring, Inc., 10420 Little Patuxent Pkwy, Suite 250, 21044, Columbia, Maryland, USA;

关键词: Retina;    Rod photoreceptor;    Cngb1a;    cGMP-gated cation channel;    Phototransduction;   

DOI  :  10.1186/s12964-014-0067-5

 received in 2014-05-15, accepted in 2014-10-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe rod photoreceptor cGMP-gated cation channel, consisting of three α- and one β subunit, controls ion flow into the rod outer segment (ROS). In addition to the β-subunit, the Cngb1 locus encodes an abundant soluble protein, GARP2 that binds stoichiometrically to rod photoreceptor cGMP phosphodiesterase type 6 (PDE6). To examine the in vivo functional role of GARP2 we generated opsin promoter-driven transgenic mice overexpressing GARP2 three-fold specifically in rod photoreceptors.ResultsIn the GARP2 overexpressing transgenic mice (tg), the endogenous channel β-subunit, cGMP phosphodiesterase α-subunit, peripherin2/RDS and guanylate cyclase I were present at WT levels and were properly localized within the ROS. While localized properly within ROS, two proteins cGMP phosphodiesterase α-subunit (1.4-fold) and cGMP-gated cation channel α-subunit (1.2-fold) were moderately, but significantly elevated. Normal stratification of all retinal layers was observed, and ROS were stable in numbers but were 19% shorter than WT. Analysis of the photoresponse using electroretinography (ERG) showed that tg mice exhibit no change in sensitivity indicating overall normal rod function, however two parameters of the photoresponse significantly differed from WT responses. Fitting of the rising phase of the ERG a-wave to an accepted model of phototransduction showed a two-fold increase in phototransduction gain in the tg mice. The increase in gain was confirmed in isolated retinal tissue and by suction electrode recordings of individual rod photoreceptor cells. A measure of response recovery, the dominant time constant (τD) was elevated 69% in isolated retina compared to WT, indicating slower shutoff of the photoresponse.ConclusionsGARP2 may participate in regulating visual signal transduction through a previously unappreciated role in regulating phototransduction gain and recovery.

【 授权许可】

Unknown   
© Sarfare et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.