QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online April 1, 2009
doi: 10.1242/10.1242/jcs.042531

This Article Figures Only Full Text Full Text (PDF) Supplementary Material An erratum has been published Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, Y. Articles by Pittler, S. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Pittler, S. J. Social Bookmarking                         What's this?

Knockout of GARPs and the β-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity

¹ Department of Vision Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA
² Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
³ Department of Physiological Science, Jules Stein Eye Institute, UCLA School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
⁴ Department of Ophthalmology, Jules Stein Eye Institute, UCLA School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA

^* Author for correspondence (e-mail: pittler{at}uab.edu)

Accepted 3 December 2008

Ion flow into the rod photoreceptor outer segment (ROS) is regulated by a member of the cyclic-nucleotide-gated cation-channel family; this channel consists of two subunit types, and β. In the rod cells, the Cngb1 locus encodes the channel β-subunit and two related glutamic-acid-rich proteins (GARPs). Despite intensive research, it is still unclear why the β-subunit and GARPs are coexpressed and what function these proteins serve. We hypothesized a role for the proteins in the maintenance of ROS structural integrity. To test this hypothesis, we created a Cngb1 5'-knockout photoreceptor null (Cngb1-X1). Morphologically, ROSs were shorter and, in most rods that were examined, some disks were misaligned, misshapen and abnormally elongated at periods when stratification was still apparent and degeneration was limited. Additionally, a marked reduction in the level of channel -subunit, guanylate cyclase I (GC1) and ATP-binding cassette transporter (ABCA4) was observed without affecting levels of other ROS proteins, consistent with a requirement for the β-subunit in channel assembly or targeting of select proteins to ROS. Remarkably, phototransduction still occurred when only trace levels of homomeric -subunit channels were present, although rod sensitivity and response amplitude were both substantially reduced. Our results demonstrate that the β-subunit and GARPs are necessary not only to maintain ROS structural integrity but also for normal disk morphogenesis, and that the β-subunit is required for normal light sensitivity of the rods.

Key words: Photoreceptor, Cyclic-nucleotide-gated channel, Cngb1 knockout

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?