Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Autistic Disorder
/ genetics
Brain
/ cytology
COS Cells
Cell Adhesion Molecules, Neuronal
/ metabolism
Cells, Cultured
Chlorocebus aethiops
Excitatory Postsynaptic Potentials
Female
Gene Deletion
Inhibitory Postsynaptic Potentials
Male
Membrane Proteins
/ metabolism
Mice
Mice, Inbred C57BL
Miniature Postsynaptic Potentials
Nerve Tissue Proteins
/ metabolism
Rats
Rats, Sprague-Dawley
Receptors, GABA
/ metabolism
Schizophrenia
/ genetics
Synapses
/ metabolism
15q11.2
ASD
CNV
GABA
dendritic spine
epilepsy
excitatory/inhibitory
gephyrin
microdeletion
microduplication
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
19 02 2019
19 02 2019
Historique:
received:
20
04
2018
revised:
26
10
2018
accepted:
24
01
2019
entrez:
21
2
2019
pubmed:
21
2
2019
medline:
11
4
2020
Statut:
ppublish
Résumé
Altered excitatory/inhibitory (E/I) balance is implicated in neuropsychiatric and neurodevelopmental disorders, but the underlying genetic etiology remains poorly understood. Copy number variations in CYFIP1 are associated with autism, schizophrenia, and intellectual disability, but its role in regulating synaptic inhibition or E/I balance remains unclear. We show that CYFIP1, and the paralog CYFIP2, are enriched at inhibitory postsynaptic sites. While CYFIP1 or CYFIP2 upregulation increases excitatory synapse number and the frequency of miniature excitatory postsynaptic currents (mEPSCs), it has the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Contrary to CYFIP1 upregulation, its loss in vivo, upon conditional knockout in neocortical principal cells, increases expression of postsynaptic GABA
Identifiants
pubmed: 30784587
pii: S2211-1247(19)30129-9
doi: 10.1016/j.celrep.2019.01.092
pmc: PMC6381785
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cell Adhesion Molecules, Neuronal
0
Cyfip1 protein, mouse
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Receptors, GABA
0
neuroligin 3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2037-2051.e6Subventions
Organisme : European Research Council
ID : 282430
Pays : International
Organisme : Medical Research Council
ID : G0802377
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K015826/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N025644/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Mol Psychiatry. 2014 Jul;19(7):784-90
pubmed: 23999528
PLoS One. 2011;6(4):e18556
pubmed: 21602908
Cell. 2014 Jan 16;156(1-2):195-207
pubmed: 24439376
Neuron. 2010 Jan 14;65(1):53-65
pubmed: 20152113
Cell Rep. 2017 Oct 3;21(1):70-83
pubmed: 28978485
Nat Genet. 2017 Jan;49(1):27-35
pubmed: 27869829
Nature. 2010 Nov 25;468(7323):533-8
pubmed: 21107423
Neuron. 2009 Jun 11;62(5):670-82
pubmed: 19524526
Am J Med Genet B Neuropsychiatr Genet. 2016 Dec;171(8):1088-1098
pubmed: 27566550
Transl Psychiatry. 2014 Mar 25;4:e374
pubmed: 24667445
Nature. 2014 Feb 13;506(7487):179-84
pubmed: 24463507
Am J Hum Genet. 2014 May 1;94(5):677-94
pubmed: 24768552
J Neurosci. 2005 Mar 30;25(13):3379-88
pubmed: 15800193
Neuron. 2015 Aug 19;87(4):684-98
pubmed: 26291155
Biochem Soc Trans. 2010 Apr;38(2):445-51
pubmed: 20298200
Mol Psychiatry. 2015 Sep;20(9):1069-78
pubmed: 25311365
PLoS One. 2016 Jan 29;11(1):e0148039
pubmed: 26824476
Ann Hum Genet. 2015 Sep;79(5):329-340
pubmed: 26094621
Neuron. 2013 Sep 18;79(6):1169-82
pubmed: 24050404
Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2551-6
pubmed: 25675530
Hum Genet. 2017 Nov;136(11-12):1419-1429
pubmed: 28940097
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16679-84
pubmed: 20823221
J Cell Biol. 2013 Jun 10;201(6):929-44
pubmed: 23751499
Trends Neurosci. 2015 Aug;38(8):496-505
pubmed: 26209464
Curr Mol Med. 2015;15(2):146-67
pubmed: 25732149
Cell. 2014 Jan 16;156(1-2):208-20
pubmed: 24439377
J Neurochem. 2017 Jun;141(6):819-834
pubmed: 28199019
Eur J Med Genet. 2009 Mar-Jun;52(2-3):108-15
pubmed: 19328872
Neuron. 2013 Jul 24;79(2):293-307
pubmed: 23889934
Eur J Neurosci. 2007 Oct;26(7):1738-48
pubmed: 17897391
Science. 2013 Dec 20;342(6165):1508-12
pubmed: 24357318
J Neurosci. 2017 Nov 15;37(46):11127-11139
pubmed: 29030434
Neuron. 2009 Sep 10;63(5):628-42
pubmed: 19755106
Mol Psychiatry. 2017 Oct;22(10):1483-1491
pubmed: 27725662
Biol Psychiatry. 2017 May 1;81(9):757-769
pubmed: 27914629
Eur J Cell Biol. 2004 Sep;83(9):449-56
pubmed: 15540461
EMBO Rep. 2017 Feb;18(2):231-240
pubmed: 28039205
Nature. 2011 Jun 15;474(7351):337-42
pubmed: 21677750
Genesis. 2006 Dec;44(12):611-21
pubmed: 17146780
EMBO J. 2011 Feb 2;30(3):569-81
pubmed: 21217644
Cell Rep. 2014 Oct 9;9(1):298-310
pubmed: 25284783
Science. 2007 Oct 5;318(5847):71-6
pubmed: 17823315
Neuron. 2013 May 8;78(3):510-22
pubmed: 23664616
J Neurosci. 2016 Feb 3;36(5):1564-76
pubmed: 26843638
J Biol Chem. 2016 Jan 8;291(2):613-29
pubmed: 26553875
Cell Rep. 2016 Oct 4;17(2):317-327
pubmed: 27705781
Mol Biol Cell. 2016 Nov 1;27(21):3342-3356
pubmed: 27605705
Brain. 2016 Oct;139(Pt 10):2751-2765
pubmed: 27524794
Annu Rev Pharmacol Toxicol. 2014;54:483-507
pubmed: 24160694
Cell Stem Cell. 2014 Jul 3;15(1):79-91
pubmed: 24996170
Nature. 2013 Jan 17;493(7432):371-7
pubmed: 23172145
Nature. 2014 Nov 13;515(7526):209-15
pubmed: 25363760
Cell. 2008 Sep 19;134(6):1042-54
pubmed: 18805096
Brain. 2010 Jan;133(Pt 1):23-32
pubmed: 19843651
J Neurosci. 2017 Dec 6;37(49):11993-12005
pubmed: 29118110
Science. 2016 Sep 9;353(6304):1123-9
pubmed: 27609886
Neurosci Lett. 2015 Aug 5;601:30-40
pubmed: 25578949
J Physiol. 2008 Feb 15;586(4):965-87
pubmed: 18063661
Genes Brain Behav. 2009 Feb;8(1):114-26
pubmed: 19016888
Biol Psychiatry. 2017 May 15;81(10):848-861
pubmed: 28434615
Cell. 2011 Jul 22;146(2):247-61
pubmed: 21784246
Nature. 2014 Nov 13;515(7526):216-21
pubmed: 25363768
Nat Cell Biol. 2010 Apr;12(4):330-40
pubmed: 20228810
Nat Rev Neurosci. 2015 Sep;16(9):551-63
pubmed: 26289574
Br J Psychiatry. 2014 Feb;204(2):108-14
pubmed: 24311552
Am J Med Genet B Neuropsychiatr Genet. 2010 Jun 5;153B(4):960-6
pubmed: 20029941
Mol Psychiatry. 2015 Apr;20(4):424-32
pubmed: 25048004
Nat Genet. 2003 May;34(1):27-9
pubmed: 12669065
Nature. 2010 Nov 11;468(7321):263-9
pubmed: 21068835
Ann Neurol. 2018 Apr;83(4):794-806
pubmed: 29534297
Nat Rev Neurosci. 2014 Mar;15(3):141-56
pubmed: 24552784
Dis Model Mech. 2017 Apr 1;10(4):463-474
pubmed: 28183735
Nature. 2008 Sep 11;455(7210):232-6
pubmed: 18668039
J Neurosci. 2017 Jul 19;37(29):6816-6836
pubmed: 28607166
Nat Methods. 2011 Jun 05;8(7):571-3
pubmed: 21642963
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):589-594
pubmed: 29295931
Neuron. 2017 Mar 8;93(5):1138-1152.e6
pubmed: 28279354
Nature. 2011 Jul 27;477(7363):171-8
pubmed: 21796121
Hum Mol Genet. 2007 Jul 15;16(14):1682-98
pubmed: 17519220
Int J Neurosci. 2016 Jun;126(6):542-551
pubmed: 26000921
Neuron. 2013 Oct 2;80(1):113-28
pubmed: 24094106
PLoS One. 2012;7(8):e42422
pubmed: 22900020
Eur J Med Genet. 2015 Mar;58(3):140-7
pubmed: 25596525
PLoS Genet. 2012 Feb;8(2):e1002521
pubmed: 22346768
J Neurosci. 2017 Jul 26;37(30):7096-7110
pubmed: 28630256
Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1100-5
pubmed: 9927700
EMBO J. 2018 Feb 1;37(3):321-336
pubmed: 29311115
Hum Mol Genet. 2015 Apr 1;24(7):1813-23
pubmed: 25432536
J Biol Chem. 1998 Jan 2;273(1):291-5
pubmed: 9417078