SynCAM1 recruits NMDA receptors via protein 4.1B.
Cell adhesion molecules have been implicated as key organizers of synaptic structures, but there is still a need to determine how these molecules facilitate neurotransmitter receptor recruitment to developing synapses. Here, we identify erythrocyte protein band 4.1-like 3 (protein 4.1B) as an intracellular effector molecule of Synaptic Cell Adhesion Molecule 1 (SynCAM1) that is sufficient to recruit NMDA-type receptors (NMDARs) to SynCAM1 adhesion sites in COS7 cells. Protein 4.1B in conjunction with SynCAM1 also increased the frequency of NMDAR-mediated mEPSCs and area of presynaptic contact in an HEK293 cell/ neuron co-culture assay. Studies in cultured hippocampal neurons reveal that manipulation of protein 4.1B expression levels specifically affects NMDAR-mediated activity and localization. Finally, further experimentation in COS7 cells show that SynCAM1 may also interact with protein 4.1N to specifically effect AMPA type receptor (AMPAR) recruitment. Thus, SynCAM1 may recruit both AMPARs and NMDARs by independent mechanisms during synapse formation.
Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA.
Jennifer L
JL
Hoy
John R
JR
Constable
Stefano
S
Vicini
Zhanyan
Z
Fu
Philip
P
Washbourne
D000818:Animals; D001681:Biological Assay / Q000379:methods; D015415:Biomarkers / Q000378:metabolism; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007136:Immunoglobulins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008863:Microspheres; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; C465040:Cadm1 protein, rat; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C116887:EPB41L3 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D025521:Tumor Suppressor Proteins