title: MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density.
abstract: At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons. MPP2 also colocalises with the synaptic adhesion molecule SynCAM1. We demonstrate that the SynCAM1 C-terminus interacts directly with the MPP2 PDZ domain and that MPP2 does not interact in this manner with other highly abundant postsynaptic transmembrane proteins. Our results highlight a previously unexplored role for MPP2 at postsynaptic sites as a scaffold that links SynCAM1 cell adhesion molecules to core proteins of the postsynaptic density.
authors.affiliation: Neuroscience Research Center and Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Rademacher
authors.affiliation: Neuroscience Research Center and Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schmerl
authors.affiliation: Institute of Chemistry and Biochemistry, Structural Biochemistry, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lardong
authors.affiliation: Institute of Chemistry and Biochemistry, Structural Biochemistry, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Wahl
authors.affiliation: Neuroscience Research Center and Cluster of Excellence NeuroCure, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Shoichet
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D000074407:SAP90-PSD95 Associated Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics
chemical_list: C465040:Cadm1 protein, rat; D015815:Cell Adhesion Molecules; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D000074407:SAP90-PSD95 Associated Proteins