دورية أكاديمية
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EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling.

التفاصيل البيبلوغرافية
العنوان: EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling.
المؤلفون: Loucks CM; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada., Park K; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada., Walker DS; Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., McEwan AH; Djavad Mowfaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Timbers TA; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada., Ardiel EL; Djavad Mowfaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Grundy LJ; Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., Li C; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada., Johnson JL; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada., Kennedy J; School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland., Blacque OE; School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland., Schafer W; Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom., Rankin CH; Djavad Mowfaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.; Department of Psychology, University of British Columbia, Vancouver, Canada., Leroux MR; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada.; Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, Canada.
المصدر: ELife [Elife] 2019 Feb 27; Vol. 8. Date of Electronic Publication: 2019 Feb 27.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Synaptic Transmission*, Caenorhabditis elegans/*physiology , Cilia/*metabolism , Dopaminergic Neurons/*physiology , Synapses/*metabolism, Animals
مستخلص: Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, the roles of cilia in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME). We demonstrate that C. elegans EFHC-1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC-1 also localizes at the synapse, where it further modulates dopamine signaling in cooperation with the orthologue of an R-type voltage-gated calcium channel. Our findings unveil a previously undescribed dual-regulation of neuronal excitability at sites of neuronal sensory input (cilium) and neuronal output (synapse). Such a distributed regulatory mechanism may be essential for establishing neuronal activation thresholds under physiological conditions, and when impaired, may represent a novel pathomechanism for epilepsy.
Competing Interests: CL, KP, DW, AM, TT, EA, LG, CL, JJ, JK, OB, WS, CR, ML No competing interests declared
(© 2019, Loucks et al.)
References: Nat Neurosci. 2009 Oct;12(10):1266-74. (PMID: 19734894)
J Comp Neurol. 2007 Dec 10;505(5):562-71. (PMID: 17924533)
Hum Mol Genet. 2009 Mar 15;18(6):1099-109. (PMID: 19147686)
Hum Mol Genet. 2011 Nov 1;20(21):4248-57. (PMID: 21835885)
Neuron. 2001 Aug 2;31(2):277-87. (PMID: 11502258)
Neuroimage. 2010 Jun;51(2):606-15. (PMID: 20188181)
FEBS Lett. 2005 Jan 31;579(3):819-22. (PMID: 15670853)
Acta Neurol Scand. 1985 Nov;72(5):449-59. (PMID: 3936330)
Methods Cell Biol. 2008;88:411-29. (PMID: 18617045)
Exp Cell Res. 2006 Sep 10;312(15):2872-9. (PMID: 16824517)
Epilepsy Behav. 2007 Mar;10(2):263-7. (PMID: 17258506)
Neurology. 2008 Sep 9;71(11):788-94. (PMID: 18463366)
Mol Neurobiol. 2018 Jun;55(6):4513-4528. (PMID: 28685386)
Nat Neurosci. 2009 Oct;12(10):1257-65. (PMID: 19718034)
Biochem Biophys Res Commun. 2008 Feb 29;367(1):226-33. (PMID: 18164683)
Nat Methods. 2013 Sep;10(9):877-9. (PMID: 23852451)
Nat Methods. 2011 Jun 05;8(7):592-8. (PMID: 21642964)
J Neurosci. 2003 Jul 23;23(16):6537-45. (PMID: 12878695)
Epilepsy Curr. 2007 May-Jun;7(3):61-7. (PMID: 17520076)
Genetics. 2015 Aug;200(4):1035-49. (PMID: 26044593)
J Mol Neurosci. 2009 Sep;39(1-2):69-77. (PMID: 19191033)
Elife. 2019 Feb 27;8:. (PMID: 30810526)
J Neurosci. 1997 Nov 1;17(21):8061-73. (PMID: 9334382)
J Biol Chem. 2003 Feb 28;278(9):7725-34. (PMID: 12435737)
Neuron. 2000 Jun;26(3):619-31. (PMID: 10896158)
Epilepsia. 2000 Apr;41(4):426-31. (PMID: 10756408)
Curr Biol. 2013 Jun 3;23(11):963-7. (PMID: 23707432)
Neuron. 2007 Aug 16;55(4):662-76. (PMID: 17698017)
Methods Cell Biol. 2015;127:323-47. (PMID: 25837399)
J Neurosci. 2005 Jun 22;25(25):5975-83. (PMID: 15976086)
J Biol Chem. 2014 Jun 20;289(25):17427-44. (PMID: 24794867)
Neuron. 2010 Aug 12;67(3):381-91. (PMID: 20696377)
Ann Neurol. 1984;16 Suppl:S145-58. (PMID: 6150683)
Nature. 1995 May 4;375(6526):73-8. (PMID: 7723846)
Hum Mol Genet. 2012 Dec 1;21(23):5106-17. (PMID: 22926142)
Cell Calcium. 2012 Feb;51(2):179-85. (PMID: 22226147)
Acad Emerg Med. 2011 Oct;18(10):1099-104. (PMID: 21996075)
Neurology. 1996 Nov;47(5):1203-12. (PMID: 8909431)
Curr Opin Cell Biol. 2016 Apr;39:84-92. (PMID: 26926036)
Philos Trans R Soc Lond B Biol Sci. 1986 Nov 12;314(1165):1-340. (PMID: 22462104)
J Neurosci. 2007 Dec 19;27(51):14216-27. (PMID: 18094261)
Nat Neurosci. 2004 Oct;7(10):1096-103. (PMID: 15378064)
Behav Brain Res. 1990 Feb 12;37(1):89-92. (PMID: 2310497)
J Comp Neurol. 1975 Sep 15;163(2):215-26. (PMID: 240872)
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2227-31. (PMID: 8460126)
Nat Genet. 2004 Aug;36(8):842-9. (PMID: 15258581)
Neuroimage. 2012 Feb 15;59(4):3582-93. (PMID: 22056530)
PLoS Genet. 2012;8(11):e1003015. (PMID: 23166505)
Dev Biol. 2016 Mar 15;411(2):257-265. (PMID: 26783883)
WormBook. 2007 Mar 08;:1-22. (PMID: 18050505)
Nature. 2001 Jul 19;412(6844):338-41. (PMID: 11460165)
Neuropsychiatry Neuropsychol Behav Neurol. 1997 Oct;10(4):243-6. (PMID: 9359121)
Nat Neurosci. 2007 May;10(5):568-77. (PMID: 17450139)
Mol Biol Cell. 2016 Jul 1;27(13):2133-44. (PMID: 27193298)
EMBO J. 2011 Mar 16;30(6):1110-22. (PMID: 21304491)
EMBO J. 2004 Jan 28;23(2):473-82. (PMID: 14739932)
Nature. 1995 Nov 2;378(6552):82-5. (PMID: 7477294)
PLoS Genet. 2013;9(12):e1003977. (PMID: 24339792)
Nat Methods. 2013 Aug;10(8):741-3. (PMID: 23817069)
Front Cell Neurosci. 2013 Sep 17;7:157. (PMID: 24062645)
معلومات مُعتمدة: MC_U105185857 United Kingdom MRC_ Medical Research Council; Frederick Banting and Charles Best Canada Graduate Scholarship Canada CIHR; 11/PI/1037 Ireland SFI_ Science Foundation Ireland; Senior Scholar Award International Michael Smith Foundation for Health Research; MOP82870 Canada CIHR; MC_A023_5PB91 United Kingdom MRC_ Medical Research Council; MOP130287 Canada CIHR; Vanier Canada Graduate Scholarship International Natural Sciences and Engineering Research Council of Canada; Discover Grant 122216-2013 International Natural Sciences and Engineering Research Council of Canada; WT103784MA International Wellcome
فهرسة مساهمة: Keywords: C. elegans; Caenorhabditis elegans; EFHC1; cell biology; cilia; juvenile myoclonic epilepsy; neuroscience; synapse
تواريخ الأحداث: Date Created: 20190228 Date Completed: 20200330 Latest Revision: 20210109
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6392500
DOI: 10.7554/eLife.37271
PMID: 30810526
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.37271