A new subunit of the cyclic nucleotide-gated cation channel in retinal rods

Abstract

Retinal rods respond to light with a membrane hyperpolarization produced by a G-protein-mediated signalling cascade that leads to cyclic GMP hydrolysis and the consequent closure of a cGMP-gated channel that is open in darkness. A protein that forms this channel has recently been purified from bovine retina and molecularly cloned, suggesting that the native cGMP-gated channel might be a homo-oligomer. Here we report the cloning of another protein from human retina which has only about 30% overall identity to the rod channel subunit. This protein, immunocytochemically localized to rod outer segments, does not form functional channels by itself. However, when co-expressed with the cloned human rod channel protein, it introduces rapid flickers to the channel openings that are characteristic of the native channel. The hetero-oligomeric channel is also highly sensitive to the blocker L-cis-diltiazem, like the native channel. This new protein thus seems to be another subunit of the native rod channel. The hetero-oligomeric nature of the rod channel means that it is no exception to a common motif shared by other ligand-gated channels.

Primary structure and functional expression of a cyclic nucleotidegated channel from rabbit aorta

“…In rabbit tissues the ligand affinity may be modified by the presence of additional channel subunits. Recently, a new subunit of the photoreceptor channel has been identified [9] which affected the sensitivity of the photoreceptor channel for L-CL+ diltiazem. Possibly other CNG channels also have a hetero-oligomeric structure.…”

“…The primary structure of these channels has been determined by molecular cloning of the corresponding cDNAs [2X3]. Recently, a novel subunit of the rod photoreceptor channel has been identified [9]. In addition, partial sequences being highly homologous to photor~ptor and olfactory channels have been amplified by PCR from kidney [IO] and heart [ 1 I], respectively.…”

Molecular cloning, functional expression and chromosomal localization of a human homolog of the cyclic nucleotide‐gated ion channel of retinal cone photoreceptors

“…The high sensitivity of the native rod channel to L-cisdiltiazem is now known to be conferred by a [3-subunit coupled to the ~-subunit [19,22]. The same may be true for the native cone channel [25].…”

“…Finally, both the human and bovine [18,25] channel homologs showed little sensitivity to L-Cis-diltiazem, unlike the native cone channel in fish [42]. This difference suggests the presence of a ]3-subunit in the native cone channel complex that is responsible for the high sensitivity to t-cis-diltiazem [25], as is the case for the native rod channel [19,22]. Whether a cone [3-subunit distinct from that in rods exists remains to be determined.…”

Impaired Channel Targeting and Retinal Degeneration in Mice Lacking the Cyclic Nucleotide-Gated Channel Subunit CNGB1

“…The CNGB1 gene locus consists of at least 33 exons encoding several isoforms (Ardell et al, 2000). Rods express a 240 kDa isoform (CNGB1a) containing a long cytosolic N terminus that is also translated as a separate cytosolic protein [glutamic acid-rich protein (GARP) (Chen et al, 1993;Körschen et al, 1995)]. Shorter variants of the subunit lacking the GARP part are present in the native olfactory CNG channel (CNGB1b) (Sautter et al, 1998;Bönigk et al, 1999) and have been identified in sperm cells and other tissues (Biel et al, 1996;Wiesner et al, 1998).…”