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Front Mol Neurosci. 2017 Jan 31;10:24. doi: 10.3389/fnmol.2017.00024. eCollection 2017.

Redundant Postsynaptic Functions of SynCAMs 1-3 during Synapse Formation.

Author information

1
Department of Biology, Institute of Neuroscience, University of OregonEugene, OR, USA; Department of Integrative Physiology and Neuroscience, Washington State UniversityPullman, WA, USA.
2
Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA.
3
Department of Biology, Institute of Neuroscience, University of Oregon Eugene, OR, USA.

Abstract

Investigating the roles of synaptogenic adhesion molecules during synapse formation has proven challenging, often due to compensatory functions between additional family members. The synaptic cell adhesion molecules 1-3 (SynCAM1-3) are expressed both pre- and postsynaptically, share highly homologous domains and are synaptogenic when ectopically presented to neurons; yet their endogenous functions during synaptogenesis are unclear. Here we report that SynCAM1-3 are functionally redundant and collectively necessary for synapse formation in cultured hippocampal neurons. Only triple knockdown (KD) of SynCAM1-3 using highly efficient, chained artificial microRNAs (amiRNAs) reduced synapse density and increased synapse area. Electrophysiological recordings of quantal release events supported an increase in synapse size caused by SynCAM1-3 depletion. Furthermore, a combinatorial, mosaic lentiviral approach comparing wild type (WT) and SynCAM1-3 KD neurons in the same culture demonstrate that SynCAM1-3 set synapse number and size through postsynaptic mechanisms. The results demonstrate that the redundancy between SynCAM1-3 has concealed their synaptogenic function at the postsynaptic terminal.

KEYWORDS:

SynCAM; adhesion; artificial miRNA; hippocampus; knockdown; mosaic; redundancy; synapse formation

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