PMID- 28197078 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5099 (Print) IS - 1662-5099 (Electronic) IS - 1662-5099 (Linking) VI - 10 DP - 2017 TI - Redundant Postsynaptic Functions of SynCAMs 1-3 during Synapse Formation. PG - 24 LID - 10.3389/fnmol.2017.00024 [doi] LID - 24 AB - 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. FAU - Fowler, Daniel K AU - Fowler DK AD - Department of Biology, Institute of Neuroscience, University of OregonEugene, OR, USA; Department of Integrative Physiology and Neuroscience, Washington State UniversityPullman, WA, USA. FAU - Peters, James H AU - Peters JH AD - Department of Integrative Physiology and Neuroscience, Washington State University Pullman, WA, USA. FAU - Williams, Carly AU - Williams C AD - Department of Biology, Institute of Neuroscience, University of Oregon Eugene, OR, USA. FAU - Washbourne, Philip AU - Washbourne P AD - Department of Biology, Institute of Neuroscience, University of Oregon Eugene, OR, USA. LA - eng GR - R01 DK092651/DK/NIDDK NIH HHS/United States GR - T32 HD007348/HD/NICHD NIH HHS/United States PT - Journal Article DEP - 20170131 PL - Switzerland TA - Front Mol Neurosci JT - Frontiers in molecular neuroscience JID - 101477914 PMC - PMC5281628 OTO - NOTNLM OT - SynCAM OT - adhesion OT - artificial miRNA OT - hippocampus OT - knockdown OT - mosaic OT - redundancy OT - synapse formation EDAT- 2017/02/16 06:00 MHDA- 2017/02/16 06:01 PMCR- 2017/01/01 CRDT- 2017/02/16 06:00 PHST- 2016/12/07 00:00 [received] PHST- 2017/01/17 00:00 [accepted] PHST- 2017/02/16 06:00 [entrez] PHST- 2017/02/16 06:00 [pubmed] PHST- 2017/02/16 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fnmol.2017.00024 [doi] PST - epublish SO - Front Mol Neurosci. 2017 Jan 31;10:24. doi: 10.3389/fnmol.2017.00024. eCollection 2017.