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Original Article |
rkramer{at}chroma.med.miami.edu
The cGMP sensitivity of cyclic nucleotide–gated (CNG) channels can be modulated by changes in phosphorylation catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. Previously, we used genistein, a PTK inhibitor, to probe the interaction between PTKs and homomeric channels comprised of
subunits (RET) of rod photoreceptor CNG channels expressed in Xenopus oocytes. We showed that in addition to inhibiting phosphorylation, genistein triggers a noncatalytic interaction between PTKs and homomeric RET channels that allosterically inhibits channel gating. Here, we show that native CNG channels from rods, cones, and olfactory receptor neurons also exhibit noncatalytic inhibition induced by genistein, suggesting that in each of these sensory cells, CNG channels are part of a regulatory complex that contains PTKs. Native CNG channels are heteromers, containing β as well as subunits. To determine the contributions of and β subunits to genistein inhibition, we compared the effect of genistein on native, homomeric (RET and OLF), and heteromeric (RET+β, OLF+β, and OLF+RETβ) CNG channels. We found that genistein only inhibits channels that contain either the RET or the OLFβ subunits. This finding, along with other observations about the maximal effect of genistein and the Hill coefficient of genistein inhibition, suggests that the RET and OLFβ subunits contain binding sites for the PTK, whereas RETβ and OLF subunits do not.
Key Words: cyclic guanosine monophosphate • protein tyrosine kinase • photoreceptor • olfactory receptor neuron
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