Activity-dependent modulation of rod photoreceptor cyclic nucleotide- gated channels mediated by phosphorylation of a specific tyrosine residue

Elena Molokanova, Floyd Maddox, Charles W. Luetje, Richard H. Kramer

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Cyclic nucleotide-gated (CNG) channels are crucial for phototransduction in vertebrate rod photoreceptors. The cGMP sensitivity of these channels is modulated by diffusible intracellular messengers, including Ca2+/calmodulin, contributing to negative feedback during sensory adaptation. Membrane-associated protein tyrosine kinases and phosphatases also modulate rod CNG channels, but whether this results from direct changes in the phosphorylation state of the channel protein has been unclear. Here, we show that bovine rod CNG channel α-subunits (bRET) contain a tyrosine phosphorylation site crucial for modulation. bRET channels expressed in Xenopus oocytes exhibit modulation, whereas rat olfactory CNG channels (rOLF) do not. Chimeric channels reveal that differences in the C terminus, containing the cyclic nucleotide-binding domain, account for this difference. One specific tyrosine in bRET (Y498) appears to be crucial; replacement of this tyrosine in bRET curtails modulation, whereas installation into rOLF confers modulability. As the channel becomes dephosphorylated, there is an increase in the rate of spontaneous openings in the absence of ligand, indicating that changes in the phosphorylation state affect the allosteric gating equilibrium. Moreover, we find that dephosphorylation, which favors channel opening, requires open channels, whereas phosphorylation, which promotes channel dosing, requires closed channels. Hence, modulation by changes in tyrosine phosphorylation is activity-dependent and may constitute a positive feedback mechanism, contrasting with negative feedback systems underlying adaptation.

Original languageEnglish (US)
Pages (from-to)4786-4795
Number of pages10
JournalJournal of Neuroscience
Issue number12
StatePublished - Jun 15 1999
Externally publishedYes


  • Cyclic GMP
  • Phosphorylation
  • Phototransduction
  • Protein kinase
  • Rod photoreceptor
  • Tyrosine kinase

ASJC Scopus subject areas

  • Neuroscience(all)


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