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

Overview

Journal iScience

Publisher Cell Press

Date 2019 Sep 24

PMID 31546104

Citations 4

Authors

John Scott

Sonal Thakar

Ye Mao

Huaping Qin

Helen Hejran

Su-Yee Lee

Ting Yu

Olga Klezovitch

Hongqiang Cheng

Yongxin Mu

Sourav Ghosh

Valeri Vasioukhin

Yimin Zou

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory.

Voglewede M, Ozsen E, Ivak N, Bernabucci M, Tang R, Sun M iScience. 2024; 27(7):110308.

PMID: 39045101 PMC: 11263792. DOI: 10.1016/j.isci.2024.110308.

Polarity proteins: Shaping dendritic spines and memory.

Voglewede M, Zhang H Dev Biol. 2022; 488:68-73.

PMID: 35580729 PMC: 9953585. DOI: 10.1016/j.ydbio.2022.05.007.

Planar cell polarity signaling components are a direct target of β-amyloid-associated degeneration of glutamatergic synapses.

Feng B, Freitas A, Gorodetski L, Wang J, Tian R, Lee Y Sci Adv. 2021; 7(34).

PMID: 34407949 PMC: 8373119. DOI: 10.1126/sciadv.abh2307.

Breaking symmetry - cell polarity signaling pathways in growth cone guidance and synapse formation.

Zou Y Curr Opin Neurobiol. 2020; 63:77-86.

PMID: 32361599 PMC: 7483917. DOI: 10.1016/j.conb.2020.03.010.

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