Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions

被引：29
作者：
Connor, Steven A. [1 ]
Elegheert, Jonathan [2 ,3 ]
Xie, Yicheng [4 ]
Craig, Ann Marie [5 ,6 ]
机构：
[1] York Univ, Dept Biol, 4700 Keele St, N York, ON M3J 1P3, Canada
[2] CNRS, UMR 5297, Interdisciplinary Inst Neurosci, 146 Rue Leo Saignat, F-33076 Bordeaux, France
[3] Univ Bordeaux, 146 Rue Leo Saignat, F-33076 Bordeaux, France
[4] Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310052, Zhejiang, Peoples R China
[5] Univ British Columbia, Djavad Mowafaghian Ctr Brain Hlth, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
[6] Univ British Columbia, Dept Psychiat, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
来源：
CURRENT OPINION IN NEUROBIOLOGY | 2019年 / 57卷
基金：
加拿大健康研究院;
关键词：
ASSOCIATION ANALYSIS; INHIBITORY SYNAPSES; ADHESION; MIGRATION; MOLECULE; PROTEIN; REPLICATION; MODULATION; DISSECTION; ORGANIZERS;
D O I：
10.1016/j.conb.2019.01.002
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Synapse development depends on a dynamic balance between synapse promoters and suppressors. MDGAs, immunoglobulin superfamily proteins, negatively regulate synapse development through blocking neuroligin-neurexin interactions. Recent analyses of MDGA-neuroligin complexes revealed the structural basis of this activity and indicate that MDGAs interact with all neuroligins with differential affinities. Surprisingly, analyses of mouse mutants revealed a functional divergence, with targeted mutation of Mdga1 and Mdga2 elevating inhibitory and excitatory synapses, respectively, on hippocampal pyramidal neurons. Further research is needed to determine the synapse-specific organizing properties of MDGAs in neural circuits, which may depend on relative levels and subcellular distributions of each MDGA, neuroligin and neurexin. Behavioral deficits in Mdga mutant mice support genetic links to schizophrenia and autism spectrum disorders and raise the possibility of harnessing these interactions for therapeutic purposes.
引用
收藏
页码：71 / 80
页数：10
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