Neuroligins interact with multiple postsynaptic proteins, including Shank3 (Meyer et al., 2004). Moreover, it was shown more recently that Shank3 expression mediates transsynaptic changes in synaptic proteins and that this function depends on the formation of neurexin/neuroligin complexes (Arons et al., 2012). Accordingly, neurexin and neuroligin mutants, like Shank mutants, exhibit changes in the expression of synaptic proteins. Specifically, mice lacking Nrxn2α have reduced Munc-18 expression in hippocampal lysates (Dachtler et al., 2014). Mice lacking Nlgn1 have decreased expression of CSP, Liprin, Munc-18, Nxnα, and Nrxnβ, but increased expression of Nlgn3 and Synapsin1a in whole brain lysates (Blundell et al., 2010). As mentioned previously, Nlgn2 have decreased VGAT expression in hippocampus (Blundell et al., 2009), whereas Nlgn3R451C mutants increased VGAT and Gephyrin expression in whole brain lysates (Tabuchi et al., 2007). The Nlgn3R451C mutants also have decreased expression of PSD95, SAP102, NR2A, and NR2B in hippocampal lysates (Etherton et al., 2011a). Analysis of synaptosome and PSD fractions from neurexin and neuroligin mutant mice could be performed to determine if the changes more similar to changes observed in Shank mutants.
