Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.
Drosophila genes reaper, grim, and head-involution-defective (hid) induce apoptosis in several cellular contexts. N-terminal sequences of these proteins are highly conserved and are similar to N-terminal inactivation domains of voltage-gated potassium (K+) channels. Synthetic Reaper and Grim N terminus peptides induced fast inactivation of Shaker-type K+ channels when applied to the cytoplasmic side of the channel that was qualitatively similar to the inactivation produced by other K+ channel inactivation particles. Mutations that reduce the apoptotic activity of Reaper also reduced the synthetic peptide's ability to induce channel inactivation, indicating that K+ channel inactivation correlated with apoptotic activity. Coexpression of Reaper RNA or direct injection of full length Reaper protein caused near irreversible block of the K+ channels. These results suggest that Reaper and Grim may participate in initiating apoptosis by stably blocking K+ channels.
Avdonin
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V
Department of Physiology and Biophysics, Bowen 5660, University of Iowa, Iowa City, IA 52242, USA.
Kasuya
J
J
Ciorba
M A
MA
Kaplan
B
B
Hoshi
T
T
Iverson
L
L
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D014981:Xenopus
D017931:DNA Primers; D029721:Drosophila Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila