title: Redundant Postsynaptic Functions of SynCAMs 1-3 during Synapse Formation.
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.
authors.affiliation: Department of Biology, Institute of Neuroscience, University of OregonEugene, OR, USA; Department of Integrative Physiology and Neuroscience, Washington State UniversityPullman, WA, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Fowler
authors.affiliation: Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Peters
authors.affiliation: Department of Biology, Institute of Neuroscience, University of Oregon Eugene, OR, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: Williams
authors.affiliation: Department of Biology, Institute of Neuroscience, University of Oregon Eugene, OR, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Washbourne
keywords: SynCAM; adhesion; artificial miRNA; hippocampus; knockdown; mosaic; redundancy; synapse formation