HepaCAM controls astrocyte self-organization and coupling.
astrocyte
astrocyte development
astrocyte-synapse interaction
cell adhesion
connexin
gap junction
synapse
tiling
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
04 08 2021
04 08 2021
Historique:
received:
06
05
2020
revised:
19
04
2021
accepted:
19
05
2021
pubmed:
26
6
2021
medline:
14
8
2021
entrez:
25
6
2021
Statut:
ppublish
Résumé
Astrocytes extensively infiltrate the neuropil to regulate critical aspects of synaptic development and function. This process is regulated by transcellular interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes coordinate developmental processes among one another to parse out the synaptic neuropil and form non-overlapping territories is unknown. Here we identify a molecular mechanism regulating astrocyte-astrocyte interactions during development to coordinate astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked, astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for territory and morphological complexity in the developing mouse cortex. Furthermore, conditional deletion of Hepacam from developing astrocytes significantly impairs gap junction coupling between astrocytes and disrupts the balance between synaptic excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts in humans. Therefore, our findings suggest that disruption of astrocyte self-organization mechanisms could be an underlying cause of neural pathology.
Identifiants
pubmed: 34171291
pii: S0896-6273(21)00378-0
doi: 10.1016/j.neuron.2021.05.025
pmc: PMC8547372
mid: NIHMS1709751
pii:
doi:
Substances chimiques
Cell Adhesion Molecules, Neuron-Glia
0
Connexin 43
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2427-2442.e10Subventions
Organisme : NINDS NIH HHS
ID : F32 NS100392
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047258
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102237
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Mol Cell Proteomics. 2012 Feb;11(2):M111.007955
pubmed: 22067099
Neuron. 2006 Jul 20;51(2):171-8
pubmed: 16846852
Lancet Neurol. 2012 Nov;11(11):973-85
pubmed: 23079554
Neuron. 2016 Dec 21;92(6):1181-1195
pubmed: 27939582
Ann Neurol. 2015 Jan;77(1):114-31
pubmed: 25382142
Am J Hum Genet. 2011 Apr 8;88(4):422-32
pubmed: 21419380
Children (Basel). 2019 Feb 05;6(2):
pubmed: 30764523
Trends Neurosci. 2006 Oct;29(10):547-53
pubmed: 16938356
Cold Spring Harb Protoc. 2014 Jul 01;2014(7):741-9
pubmed: 24987137
Neuron. 2017 Nov 15;96(4):827-838.e9
pubmed: 29056295
J Neurosci Methods. 2012 Jun 15;207(2):172-80
pubmed: 22521325
Sci Rep. 2016 Nov 07;6:36218
pubmed: 27819278
J Cell Biol. 2018 Oct 1;217(10):3747-3765
pubmed: 30054448
Glia. 2019 Aug;67(8):1571-1597
pubmed: 31033049
J Physiol. 2015 Sep 15;593(18):4165-80
pubmed: 26033718
J Cell Biochem. 2009 Aug 15;107(6):1129-38
pubmed: 19507233
Nature. 2007 Aug 23;448(7156):901-7
pubmed: 17713529
J Cell Physiol. 2009 May;219(2):382-91
pubmed: 19142852
Ann Clin Transl Neurol. 2017 Jun 06;4(7):450-465
pubmed: 28695146
Science. 2018 Oct 12;362(6411):181-185
pubmed: 30309945
J Neurosci. 2014 Sep 3;34(36):11929-47
pubmed: 25186741
Cell Rep. 2021 Jun 22;35(12):109274
pubmed: 34161767
Nat Methods. 2018 Dec;15(12):1090-1097
pubmed: 30478326
Curr Opin Neurobiol. 2017 Aug;45:113-120
pubmed: 28570864
Nat Neurosci. 2015 Feb;18(2):170-81
pubmed: 25622573
Nature. 2017 Nov 8;551(7679):192-197
pubmed: 29120426
Hum Mol Genet. 2011 Aug 15;20(16):3266-77
pubmed: 21624973
J Neurosci. 2008 Mar 26;28(13):3264-76
pubmed: 18367594
Cell. 2006 Mar 24;124(6):1283-98
pubmed: 16564017
Neuron. 2016 Jan 6;89(1):37-53
pubmed: 26687838
Glia. 1991;4(5):484-94
pubmed: 1834565
Nat Neurosci. 2014 Apr;17(4):549-58
pubmed: 24584052
Philos Trans R Soc Lond B Biol Sci. 2014 Oct 19;369(1654):20130596
pubmed: 25225090
J Neurosci. 2002 Jan 1;22(1):183-92
pubmed: 11756501
Seizure. 2003 Sep;12(6):388-96
pubmed: 12915085
Cold Spring Harb Perspect Biol. 2015 Feb 06;7(9):a020370
pubmed: 25663667
Nat Commun. 2014 Mar 19;5:3475
pubmed: 24647135
Neuron. 2014 Oct 01;84(1):41-54
pubmed: 25242221
Nature. 2020 Dec;588(7837):296-302
pubmed: 33177716
Science. 2016 Sep 9;353(6304):1123-9
pubmed: 27609886
J Neurosci. 2017 Apr 26;37(17):4493-4507
pubmed: 28336567
Neuron. 2017 Sep 13;95(6):1365-1380.e5
pubmed: 28867552
J Vis Exp. 2010 Nov 16;(45):
pubmed: 21113117
Neuron. 2012 Mar 8;73(5):951-61
pubmed: 22405205
Cell. 2005 May 6;121(3):479-92
pubmed: 15882628
Neuron. 2014 Jul 16;83(2):388-403
pubmed: 25033182
J Physiol. 2017 Mar 15;595(6):1903-1916
pubmed: 27381164
J Biol Chem. 2005 Jul 22;280(29):27366-74
pubmed: 15917256
Nat Rev Neurosci. 2010 Feb;11(2):87-99
pubmed: 20087359
Curr Opin Neurobiol. 2014 Aug;27:75-81
pubmed: 24694749
J Cell Physiol. 2013 Apr;228(4):853-9
pubmed: 23042412
Nat Methods. 2019 Jan;16(1):67-70
pubmed: 30559429
Circ Res. 1998 Sep 21;83(6):629-35
pubmed: 9742058
Hum Mol Genet. 2020 May 8;29(7):1107-1120
pubmed: 31960914
Hum Mol Genet. 2013 Nov 1;22(21):4405-16
pubmed: 23793458
Nat Methods. 2014 Oct;11(10):982-4
pubmed: 25264773
Mol Biol Cell. 2013 Mar;24(6):715-33
pubmed: 23363606
Nat Methods. 2021 Apr;18(4):374-377
pubmed: 33795878
Brain. 2006 Oct;129(Pt 10):2761-72
pubmed: 16825202
J Biol Chem. 2006 Mar 24;281(12):7994-8009
pubmed: 16407179
Front Mol Neurosci. 2018 Apr 11;11:118
pubmed: 29695954