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Knockout of GARPs and the β-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity
- Publication Year :
- 2009
- Publisher :
- Company of Biologists, 2009.
-
Abstract
- 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, alpha and beta. In the rod cells, the Cngb1 locus encodes the channel beta-subunit and two related glutamic-acid-rich proteins (GARPs). Despite intensive research, it is still unclear why the beta-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 alpha-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 beta-subunit in channel assembly or targeting of select proteins to ROS. Remarkably, phototransduction still occurred when only trace levels of homomeric alpha-subunit channels were present, although rod sensitivity and response amplitude were both substantially reduced. Our results demonstrate that the beta-subunit and GARPs are necessary not only to maintain ROS structural integrity but also for normal disk morphogenesis, and that the beta-subunit is required for normal light sensitivity of the rods.
- Subjects :
- Protein subunit
Optic Disk
Optic disk
Morphogenesis
Cyclic Nucleotide-Gated Cation Channels
Down-Regulation
Nerve Tissue Proteins
Receptors, Cell Surface
Biology
Mice
Homomeric
Animals
Receptor
Vision, Ocular
Mice, Knockout
Transporter
Rod Cell Outer Segment
Anatomy
Cell Biology
Cell biology
Mice, Inbred C57BL
Guanylate Cyclase
ATP-Binding Cassette Transporters
Erratum
Photic Stimulation
Visual phototransduction
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1e5d464f1c43aa1f9ef7a01084060c92