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 journalArticle

52 Citations (Scopus)

Abstract

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
Pages (from-to)4786-4795
Number of pages10
JournalJournal of Neuroscience
Volume19
Issue number12
StatePublished - Jun 15 1999

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Cyclic Nucleotide-Gated Cation Channels
Retinal Rod Photoreceptor Cells
Tyrosine
Phosphorylation
Light Signal Transduction
Sensory Feedback
Vertebrate Photoreceptor Cells
Protein Tyrosine Phosphatases
Cyclic Nucleotides
Calmodulin
Xenopus
Protein-Tyrosine Kinases
Oocytes
Membrane Proteins
Ligands
Proteins

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activity-dependent modulation of rod photoreceptor cyclic nucleotide- gated channels mediated by phosphorylation of a specific tyrosine residue. / Molokanova, Elena; Maddox, Floyd; Luetje, Charles W; Kramer, Richard H.

In: Journal of Neuroscience, Vol. 19, No. 12, 15.06.1999, p. 4786-4795.

Research output: Contribution to journalArticle

Molokanova, Elena ; Maddox, Floyd ; Luetje, Charles W ; Kramer, Richard H. / Activity-dependent modulation of rod photoreceptor cyclic nucleotide- gated channels mediated by phosphorylation of a specific tyrosine residue. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 12. pp. 4786-4795.
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