title: The cytoplasmic domain of NrCAM binds to PDZ domains of synapse-associated proteins SAP90/PSD95 and SAP97.
abstract: NrCAM, a member of the L1 family of cell adhesion molecules, serves important functions during the development of the nervous system, e.g. in adhesion-dependent processes such as neurite outgrowth and axonal pathfinding. Complex homo- and heterophilic binding and several extracellular ligands of NrCAM have been described, but less is known about intracellular interaction partners. The cytoplasmic carboxy-terminus of NrCAM contains a typical sequence motif for binding to PDZ domains, making interactions with PDZ domain-containing scaffolding proteins quite conceivable. In this study, we identified specific interactions of the intracellular domain of NrCAM with class I PDZ domains of the membrane-associated guanylate kinases SAP90/PSD95 and SAP97. In contrast to NrCAM, the intracellular domains of the other mammalian L1 family molecules, e.g. L1, CHL1 and Neurofascin, did not interact with these PDZ domains. In transfected COS-7 cells, NrCAM-mediated recruitment of SAP97 to the plasma membrane was dependent on the PDZ binding motif. We show that NrCAM and SAP97 are colocalized, e.g. within photoreceptor terminals of the mammalian retina. In summary, our results confirm a functional PDZ domain binding motif at the carboxy-terminus of NrCAM and support potential functions of NrCAM during the assembly of highly organized protein complexes at the cell membrane.
authors.affiliation: Neurogenetics Research Group, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dirks
authors.forename: Uli
authors.initials: U
authors.lastname: Thomas
authors.forename: Dirk
authors.initials: D
authors.lastname: Montag
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013569:Synapses / Q000378:metabolism*; D014162:Transfection; D062826:Zonula Occludens-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; C000614189:Dlg1 protein, mouse; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C491151:Nrcam protein, mouse; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D051528:Guanylate Kinases