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

被引：6

作者：

Scott, John ^{[1
]}

Thakar, Sonal ^{[1
]}

Mao, Ye ^{[4
]}

Qin, Huaping ^{[1
]}

Hejran, Helen ^{[1
]}

Lee, Su-Yee ^{[1
]}

Yu, Ting ^{[1
]}

Klezovitch, Olga ^{[2
]}

Cheng, Hongqiang ^{[4
]}

Mu, Yongxin ^{[4
]}

Ghosh, Sourav ^{[3
]}

Vasioukhini, Valeri ^{[2
]}

Zou, Yimin ^{[1
]}

机构：

[1] Univ Calif San Diego, Biol Sci Div, Neurobiol Sect, La Jolla, CA 92093 USA

[2] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

[3] Yale Univ, Dept Neurol, New Haven, CT 06511 USA

[4] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

来源：

ISCIENCE | 2019年 / 20卷

关键词：

SMITH-MAGENIS-SYNDROME; MALADAPTIVE BEHAVIOR; DENDRITIC SPINES; PHENOTYPE; PROTEIN; CHILDREN; DELETION; COMPLEX; AUTISM; GENE;

D O I：

10.1016/j.isci.2019.09.005

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Normal synapse formation is fundamental to brain function. We showhere 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.

引用

页码：25 / +

页数：31

共 5 条

[1] Apical-basal polarity and the control of epithelial form and function
Buckley, Clare E.
St Johnston, Daniel
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2022, 23 (08) : 559 - 577
[2] PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity
Moreira, Sofia
Osswald, Mariana
Ventura, Guilherme
Goncalves, Margarida
Sunkel, Claudio E.
Morais-de-Sa, Eurico
CELL REPORTS, 2019, 26 (02): : 293 - +
[3] DECREASED EXPRESSION OF APICAL-BASAL POLARITY GENES SCRIBBLE AND LGL2 IS ASSOCIATED WITH ABNORMAL TROPHOBLAST FUNCTION: POTENTIAL IMPLICATIONS IN THE AETIOLOGY OF HUMAN FETAL GROWTH RESTRICTION.
Sutton, Emma
Yong, Hannah
Kalionis, Bill
Murthi, Padma
PLACENTA, 2021, 112 : E87 - E88
[4] PP2A Antagonizes Phosphorylation of Bazooka by PAR-1 to Control Apical-Basal Polarity in Dividing Embryonic Neuroblasts
Krahn, Michael P.
Egger-Adam, Diane
Wodarz, Andreas
DEVELOPMENTAL CELL, 2009, 16 (06) : 901 - 908
[5] PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts
Krahn, Michael P.
Wodarz, Andreas
MECHANISMS OF DEVELOPMENT, 2009, 126 : S146 - S146

← 1 →