title: Synapse associated protein 102 (SAP102) binds the C-terminal part of the scaffolding protein neurobeachin.
abstract: Neurobeachin (Nbea) is a multidomain scaffold protein abundant in the brain, where it is highly expressed during development. Nbea-null mice have severe defects in neuromuscular synaptic transmission resulting in lethal paralysis of the newborns. Recently, it became clear that Nbea is important also for the functioning of central synapses, where it is suggested to play a role in trafficking membrane proteins to both, the pre- and post-synaptic sites. So far, only few binding partners of Nbea have been found and the precise mechanism of their trafficking remains unclear. Here, we used mass spectrometry to identify SAP102, a MAGUK protein implicated in trafficking of the ionotropic glutamate AMPA- and NMDA-type receptors during synaptogenesis, as a novel Nbea interacting protein in mouse brain. Experiments in heterologous cells confirmed this interaction and revealed that SAP102 binds to the C-terminal part of Nbea that contains the DUF, PH, BEACH and WD40 domains. Furthermore, we discovered that introducing a mutation in Nbea's PH domain, which disrupts its interaction with the BEACH domain, abolishes this binding, thereby creating an excellent starting point to further investigate Nbea-SAP102 function in the central nervous system.
authors: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors: Juliane
authors: J
authors: Lauks
authors: Patricia
authors: P
authors: Klemmer
authors: Fatima
authors: F
authors: Farzana
authors: Ramesh
authors: R
authors: Karupothula
authors: Robbert
authors: R
authors: Zalm
authors: Nancy E
authors: NE
authors: Cooke
authors: Ka Wan
authors: KW
authors: Li
authors: August B
authors: AB
authors: Smit
authors: Ruud
authors: R
authors: Toonen
authors: Matthijs
authors: M
authors: Verhage
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C116869:DLG3 protein, human; D008565:Membrane Proteins; C498595:NBEA protein, human; C403265:Nbea protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C491075:Dlgh3 protein, mouse; D051528:Guanylate Kinases