Identification of MAGUK scaffold proteins as intracellular binding partners of synaptic adhesion protein Slitrk2

Publication date: Available online 8 January 2020Source: Molecular and Cellular NeuroscienceAuthor(s): Connor Loomis, Aliyah Stephens, Remi Janicot, Usman Baqai, Laura Drebushenko, Jennifer RoundAbstractSynaptic adhesion proteins play a critical role in the formation and maintenance of synapses in the developing nervous system. Errors in synaptic adhesion constitute the molecular basis of many neuropsychiatric disorders, including schizophrenia, bipolar disorder, Tourette syndrome, and autism. Slit- and Trk-like proteins (Slitrks) are a family of leucine-rich repeat containing transmembrane proteins that promote synaptogenesis. These proteins localize to the postsynaptic density, where they induce synapse formation via trans-synaptic interactions with receptor protein tyrosine phosphatases. While trans-synaptic binding partners of Slitrks have been reported, little is known about the intracellular proteins that associate with Slitrks. Here we report an interaction between Slitrk2 and members of the PSD-95 subfamily of membrane associated guanylate kinases (MAGUKs). Coimmunoprecipitation from postnatal mouse brain indicates that PSD-93 and PSD-95 associate with Slitrk2 in vivo. Mapping analysis in yeast demonstrates that Slitrk2 interacts directly with PSD-95 via a non-canonical Src homology 3 (SH3) domain binding motif that associates with the SH3 domain of PSD-95. We also show that PSD-95 induces robust clustering of Slitrk2 in 293T cells, and deletion of the SH3 domain in P...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research