AUTHOR=Fowler Daniel K. , Peters James H. , Williams Carly , Washbourne Philip 

TITLE=Redundant Postsynaptic Functions of SynCAMs 1–3 during Synapse Formation

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 10 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2017.00024

DOI=10.3389/fnmol.2017.00024

ISSN=1662-5099

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 of SynCAM1-3 using highly-efficient, chained artificial microRNAs 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 and SynCAM1-3 knockdown neurons in the same culture demonstrate that SynCAM1-3 set synapse number and size through postsynaptic mechanisms. The results demonstrate that redundancy between SynCAM1-3 has concealed their synaptogenic function at the postsynaptic terminal.