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

J Cell Sci. 2009 Apr 15;122(Pt 8):1192-200. doi: 10.1242/jcs.042531.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / deficiency*
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Down-Regulation
  • Guanylate Cyclase / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Optic Disk / enzymology
  • Optic Disk / growth & development
  • Optic Disk / metabolism*
  • Optic Disk / ultrastructure
  • Photic Stimulation
  • Receptors, Cell Surface / metabolism
  • Rod Cell Outer Segment / enzymology
  • Rod Cell Outer Segment / metabolism*
  • Rod Cell Outer Segment / ultrastructure
  • Vision, Ocular*


  • ATP-Binding Cassette Transporters
  • Abca4 protein, mouse
  • Cnga1 protein, mouse
  • Cngb1 protein, mouse
  • Cyclic Nucleotide-Gated Cation Channels
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • guanylate cyclase 1
  • Guanylate Cyclase