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PMID: 25646452 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 112 ·No. 7 ·2015-02-17 ·Pages 2245-50

Fogle KJ, Baik LS, Houl JH, Tran TT, Roberts L, Dahm NA, Cao Y, Zhou M, Holmes TC

Abstract

Blue light activation of the photoreceptor CRYPTOCHROME (CRY) evokes rapid depolarization and increased action potential firing in a subset of circadian and arousal neurons in Drosophila melanogaster. Here we show that acute arousal behavioral responses to blue light significantly differ in mutants lacking CRY, as well as mutants with disrupted opsin-based phototransduction. Light-activated CRY couples to membrane depolarization via a well conserved redox sensor of the voltage-gated potassium (K(+)) channel β-subunit (Kvβ) Hyperkinetic (Hk). The neuronal light response is almost completely absent in hk(-/-) mutants, but is functionally rescued by genetically targeted neuronal expression of WT Hk, but not by Hk point mutations that disable Hk redox sensor function. Multiple K(+) channel α-subunits that coassemble with Hk, including Shaker, Ether-a-go-go, and Ether-a-go-go-related gene, are ion conducting channels for CRY/Hk-coupled light response. Light activation of CRY is transduced to membrane depolarization, increased firing rate, and acute behavioral responses by the Kvβ subunit redox sensor.

Keywords
cryptochrome phototransduction potassium channel redox
MeSH Terms
Animals Cryptochromes/physiology Drosophila Light Signal Transduction Oxidation-Reduction Potassium Channels/physiology
Chemicals
Cryptochromes Potassium Channels
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Fogle Keri J
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Baik Lisa S
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Houl Jerry H
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Tran Tri T
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Roberts Logan
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Dahm Nicole A
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and.
Cao Yu
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030.
Zhou Ming
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030.
Holmes Todd C
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697; and tholmes@uci.edu.
References (49)
49 references, click to expand
  1. Electrical hyperexcitation of lateral ventral pacemaker neurons desynchronizes downstream circadian oscillators in the fly circadian circuit and induces multiple behavioral periods.
    J Neurosci. 2006 Jan 11;26(2):479-89 PMID: 16407545
  2. Three methionine residues located within the regulator of conductance for K+ (RCK) domains confer oxidative sensitivity to large-conductance Ca2+-activated K+ channels.
    J Physiol. 2006 Mar 1;571(Pt 2):329-48 PMID: 16396928
  3. Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto reductase.
    J Biol Chem. 2006 Jun 2;281(22):15194-200 PMID: 16569641
  4. Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons.
    Science. 2012 Aug 17;337(6096):839-42 PMID: 22859819
  5. Flavin reduction activates Drosophila cryptochrome.
    Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20455-60 PMID: 24297896
  6. Mechanism of photosignaling by Drosophila cryptochrome: role of the redox status of the flavin chromophore.
    J Biol Chem. 2014 Feb 21;289(8):4634-42 PMID: 24379403
  7. Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
    Science. 2000 Jul 7;289(5476):123-7 PMID: 10884227
  8. A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors.
    Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):705-10 PMID: 11149959
  9. The circadian clock of fruit flies is blind after elimination of all known photoreceptors.
    Neuron. 2001 Apr;30(1):249-61 PMID: 11343659
  10. Kv beta subunit oxidoreductase activity and Kv1 potassium channel trafficking.
    J Biol Chem. 2002 Mar 8;277(10):8298-305 PMID: 11748234
  11. Electrical silencing of Drosophila pacemaker neurons stops the free-running circadian clock.
    Cell. 2002 May 17;109(4):485-95 PMID: 12086605
  12. Reactive oxygen species impair Slo1 BK channel function by altering cysteine-mediated calcium sensing.
    Nat Struct Mol Biol. 2004 Feb;11(2):171-8 PMID: 14745441
  13. Excitatory and inhibitory switches for courtship in the brain of Drosophila melanogaster.
    Curr Biol. 2004 Apr 6;14(7):538-47 PMID: 15062094
  14. A constitutively active cryptochrome in Drosophila melanogaster.
    Nat Neurosci. 2004 Aug;7(8):834-40 PMID: 15258584
  15. In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia.
    Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11773-8 PMID: 15280551
  16. ATP-regulated K+ channels in cardiac muscle.
    Nature. 1983 Sep 8-14;305(5930):147-8 PMID: 6310409
  17. Voltage-sensitive potassium channels in Drosophila photoreceptors.
    J Neurosci. 1991 Oct;11(10):3079-95 PMID: 1941075
  18. Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1637-41 PMID: 8127858
  19. Shaker K+ channel beta subunits belong to an NAD(P)H-dependent oxidoreductase superfamily.
    Cell. 1994 Dec 30;79(7):1133-5 PMID: 8001150
  20. A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6763-7 PMID: 7542775
  21. JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS.
    Science. 2006 Jun 23;312(5781):1809-12 PMID: 16794082
  22. A novel photoreaction mechanism for the circadian blue light photoreceptor Drosophila cryptochrome.
    J Biol Chem. 2007 Apr 27;282(17):13011-21 PMID: 17298948
  23. Circadian- and light-dependent regulation of resting membrane potential and spontaneous action potential firing of Drosophila circadian pacemaker neurons.
    J Neurophysiol. 2008 Feb;99(2):976-88 PMID: 18077664
  24. Functional coupling between the Kv1.1 channel and aldoketoreductase Kvbeta1.
    J Biol Chem. 2008 Mar 28;283(13):8634-42 PMID: 18222921
  25. Cryptochrome is present in the compound eyes and a subset of Drosophila's clock neurons.
    J Comp Neurol. 2008 Jun 20;508(6):952-66 PMID: 18399544
  26. A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila.
    Sleep. 2008 Apr;31(4):465-72 PMID: 18457233
  27. Ultrafast dynamics and anionic active states of the flavin cofactor in cryptochrome and photolyase.
    J Am Chem Soc. 2008 Jun 18;130(24):7695-701 PMID: 18500802
  28. Circadian control of membrane excitability in Drosophila melanogaster lateral ventral clock neurons.
    J Neurosci. 2008 Jun 18;28(25):6493-501 PMID: 18562620
  29. The blue-light photoreceptor CRYPTOCHROME is expressed in a subset of circadian oscillator neurons in the Drosophila CNS.
    J Biol Rhythms. 2008 Aug;23(4):296-307 PMID: 18663237
  30. The aldo-keto reductase superfamily and its role in drug metabolism and detoxification.
    Drug Metab Rev. 2008;40(4):553-624 PMID: 18949601
  31. Large ventral lateral neurons modulate arousal and sleep in Drosophila.
    Curr Biol. 2008 Oct 28;18(20):1537-45 PMID: 18771923
  32. PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.
    Neuron. 2008 Nov 26;60(4):672-82 PMID: 19038223
  33. Light-arousal and circadian photoreception circuits intersect at the large PDF cells of the Drosophila brain.
    Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19587-94 PMID: 19060186
  34. Light-dependent interactions between the Drosophila circadian clock factors cryptochrome, jetlag, and timeless.
    Curr Biol. 2009 Feb 10;19(3):241-7 PMID: 19185492
  35. Mitochondrial superoxide radicals differentially affect muscle activity and neural function.
    Genetics. 2009 Sep;183(1):175-84 PMID: 19546321
  36. Reaction mechanism of Drosophila cryptochrome.
    Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):516-21 PMID: 21187431
  37. CRYPTOCHROME is a blue-light sensor that regulates neuronal firing rate.
    Science. 2011 Mar 18;331(6023):1409-13 PMID: 21385718
  38. Association of flavin adenine dinucleotide with the Arabidopsis blue light receptor CRY1.
    Science. 1995 Aug 18;269(5226):968-70 PMID: 7638620
  39. Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain.
    Science. 1996 Dec 20;274(5295):2089-91 PMID: 8953041
  40. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
    Nature. 1997 Jun 26;387(6636):869-75 PMID: 9202119
  41. Interaction of the K channel beta subunit, Hyperkinetic, with eag family members.
    J Biol Chem. 1998 Mar 13;273(11):6389-94 PMID: 9497369
  42. Robust circadian rhythmicity of Drosophila melanogaster requires the presence of lateral neurons: a brain-behavioral study of disconnected mutants.
    J Comp Physiol A. 1998 Apr;182(4):435-53 PMID: 9530835
  43. CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity.
    Cell. 1998 Nov 25;95(5):669-79 PMID: 9845369
  44. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila.
    Cell. 1998 Nov 25;95(5):681-92 PMID: 9845370
  45. Kvbeta1.2 subunit coexpression in HEK293 cells confers O2 sensitivity to kv4.2 but not to Shaker channels.
    J Gen Physiol. 1999 Jun;113(6):897-907 PMID: 10352037
  46. Structure of a voltage-dependent K+ channel beta subunit.
    Cell. 1999 Jun 25;97(7):943-52 PMID: 10399921
  47. The eag family of K+ channels in Drosophila and mammals.
    Ann N Y Acad Sci. 1999 Apr 30;868:356-69 PMID: 10414305
  48. Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress.
    J Biol Chem. 2004 Nov 12;279(46):47726-31 PMID: 15358777
  49. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
    Science. 2005 Aug 5;309(5736):897-903 PMID: 16002581
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1416586112
Email
tholmes@uci.edu
Published
2015-02-17
Epub
2015-00-02
Pages
2245-50
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC4343116
Subset
IM
Grants
NINDS NIH HHS · R01 NS046750 · United States
NINDS NIH HHS · NS046750 · United States
NIGMS NIH HHS · R01 GM102965 · United States
NIGMS NIH HHS · R01 GM107405 · United States
NIGMS NIH HHS · GM107405 · United States
NHLBI NIH HHS · R01 HL086392 · United States
NCI NIH HHS · CA-62203 · United States
NIGMS NIH HHS · GM102965 · United States
NCI NIH HHS · P30 CA062203 · United States
NHLBI NIH HHS · HL086392 · United States
External Links
PubMed source DOI: 10.1073/pnas.1416586112 PMC Full Text View journal details
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