A new subunit of the cyclic nucleotide-gated cation channel in retinal rods.
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.
Chen
T Y
TY
Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Peng
Y W
YW
Dhallan
R S
RS
Ahamed
B
B
Reed
R R
RR
Yau
K W
KW
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels; D004110:Diltiazem / Q000494:pharmacology; D004563:Electrochemistry; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D012374:Rod Cell Outer Segment / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D014981:Xenopus
D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins; D007473:Ion Channels; D004110:Diltiazem; D006152:Cyclic GMP