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Curr Opin Neurobiol. 2019 Feb 13;57:71-80. doi: 10.1016/j.conb.2019.01.002. [Epub ahead of print]

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

Author information

1
Department of Biology, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada. Electronic address: saconnor@yorku.ca.
2
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297 and University of Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, France.
3
The Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
4
Djavad Mowafaghian Centre for Brain Health and Department of Psychiatry, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. Electronic address: acraig@mail.ubc.ca.

Abstract

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.

PMID:
30771697
DOI:
10.1016/j.conb.2019.01.002

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