Cargando…

Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function

Normal synapse formation is fundamental to brain function. We show here that an apical-basal polarity (A-BP) protein, Lgl1, is present in the postsynaptic density and negatively regulates glutamatergic synapse numbers by antagonizing the atypical protein kinase Cs (aPKCs). A planar cell polarity pro...

Descripción completa

Detalles Bibliográficos
Autores principales: Scott, John, Thakar, Sonal, Mao, Ye, Qin, Huaping, Hejran, Helen, Lee, Su-Yee, Yu, Ting, Klezovitch, Olga, Cheng, Hongqiang, Mu, Yongxin, Ghosh, Sourav, Vasioukhin, Valeri, Zou, Yimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817635/
https://www.ncbi.nlm.nih.gov/pubmed/31546104
http://dx.doi.org/10.1016/j.isci.2019.09.005
_version_ 1783463464446984192
author Scott, John
Thakar, Sonal
Mao, Ye
Qin, Huaping
Hejran, Helen
Lee, Su-Yee
Yu, Ting
Klezovitch, Olga
Cheng, Hongqiang
Mu, Yongxin
Ghosh, Sourav
Vasioukhin, Valeri
Zou, Yimin
author_facet Scott, John
Thakar, Sonal
Mao, Ye
Qin, Huaping
Hejran, Helen
Lee, Su-Yee
Yu, Ting
Klezovitch, Olga
Cheng, Hongqiang
Mu, Yongxin
Ghosh, Sourav
Vasioukhin, Valeri
Zou, Yimin
author_sort Scott, John
collection PubMed
description Normal synapse formation is fundamental to brain function. We show here that an apical-basal polarity (A-BP) protein, Lgl1, is present in the postsynaptic density and negatively regulates glutamatergic synapse numbers by antagonizing the atypical protein kinase Cs (aPKCs). A planar cell polarity protein, Vangl2, which inhibits synapse formation, was decreased in synaptosome fractions of cultured cortical neurons from Lgl1 knockout embryos. Conditional knockout of Lgl1 in pyramidal neurons led to reduction of AMPA/NMDA ratio and impaired plasticity. Lgl1 is frequently deleted in Smith-Magenis syndrome (SMS). Lgl1 conditional knockout led to increased locomotion, impaired novel object recognition and social interaction. Lgl1+/− animals also showed increased synapse numbers, defects in open field and social interaction, as well as stereotyped repetitive behavior. Social interaction in Lgl1+/− could be rescued by NMDA antagonists. Our findings reveal a role of apical-basal polarity proteins in glutamatergic synapse development and function and also suggest a potential treatment for SMS patients with Lgl1 deletion.
format Online
Article
Text
id pubmed-6817635
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-68176352019-10-31 Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function Scott, John Thakar, Sonal Mao, Ye Qin, Huaping Hejran, Helen Lee, Su-Yee Yu, Ting Klezovitch, Olga Cheng, Hongqiang Mu, Yongxin Ghosh, Sourav Vasioukhin, Valeri Zou, Yimin iScience Article Normal synapse formation is fundamental to brain function. We show here that an apical-basal polarity (A-BP) protein, Lgl1, is present in the postsynaptic density and negatively regulates glutamatergic synapse numbers by antagonizing the atypical protein kinase Cs (aPKCs). A planar cell polarity protein, Vangl2, which inhibits synapse formation, was decreased in synaptosome fractions of cultured cortical neurons from Lgl1 knockout embryos. Conditional knockout of Lgl1 in pyramidal neurons led to reduction of AMPA/NMDA ratio and impaired plasticity. Lgl1 is frequently deleted in Smith-Magenis syndrome (SMS). Lgl1 conditional knockout led to increased locomotion, impaired novel object recognition and social interaction. Lgl1+/− animals also showed increased synapse numbers, defects in open field and social interaction, as well as stereotyped repetitive behavior. Social interaction in Lgl1+/− could be rescued by NMDA antagonists. Our findings reveal a role of apical-basal polarity proteins in glutamatergic synapse development and function and also suggest a potential treatment for SMS patients with Lgl1 deletion. Elsevier 2019-09-09 /pmc/articles/PMC6817635/ /pubmed/31546104 http://dx.doi.org/10.1016/j.isci.2019.09.005 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scott, John
Thakar, Sonal
Mao, Ye
Qin, Huaping
Hejran, Helen
Lee, Su-Yee
Yu, Ting
Klezovitch, Olga
Cheng, Hongqiang
Mu, Yongxin
Ghosh, Sourav
Vasioukhin, Valeri
Zou, Yimin
Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title_full Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title_fullStr Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title_full_unstemmed Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title_short Apical-Basal Polarity Signaling Components, Lgl1 and aPKCs, Control Glutamatergic Synapse Number and Function
title_sort apical-basal polarity signaling components, lgl1 and apkcs, control glutamatergic synapse number and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817635/
https://www.ncbi.nlm.nih.gov/pubmed/31546104
http://dx.doi.org/10.1016/j.isci.2019.09.005
work_keys_str_mv AT scottjohn apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT thakarsonal apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT maoye apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT qinhuaping apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT hejranhelen apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT leesuyee apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT yuting apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT klezovitcholga apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT chenghongqiang apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT muyongxin apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT ghoshsourav apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT vasioukhinvaleri apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction
AT zouyimin apicalbasalpolaritysignalingcomponentslgl1andapkcscontrolglutamatergicsynapsenumberandfunction