TY - JOUR T1 - The Postsynaptic Adenomatous Polyposis Coli (APC) Multiprotein Complex Is Required for Localizing Neuroligin and Neurexin to Neuronal Nicotinic Synapses <em>in Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11073 LP - 11085 DO - 10.1523/JNEUROSCI.0983-10.2010 VL - 30 IS - 33 AU - Madelaine M. Rosenberg AU - Fang Yang AU - Jesse L. Mohn AU - Elizabeth K. Storer AU - Michele H. Jacob Y1 - 2010/08/18 UR - http://www.jneurosci.org/content/30/33/11073.abstract N2 - Synaptic efficacy requires that presynaptic and postsynaptic specializations align precisely and mature coordinately. The underlying mechanisms are poorly understood, however. We propose that adenomatous polyposis coli protein (APC) is a key coordinator of presynaptic and postsynaptic maturation. APC organizes a multiprotein complex that directs nicotinic acetylcholine receptor (nAChR) localization at postsynaptic sites in avian ciliary ganglion neurons in vivo. We hypothesize that the APC complex also provides retrograde signals that direct presynaptic active zones to develop in register with postsynaptic nAChR clusters. In our model, the APC complex provides retrograde signals via postsynaptic neuroligin that interacts extracellularly with presynaptic neurexin. S-SCAM (synaptic cell adhesion molecule) and PSD-93 (postsynaptic density-93) are scaffold proteins that bind to neuroligin. We identify S-SCAM as a novel component of neuronal nicotinic synapses. We show that S-SCAM, PSD-93, neuroligin and neurexin are enriched at α3*-nAChR synapses. PSD-93 and S-SCAM bind to APC and its binding partner β-catenin, respectively. Blockade of selected APC and β-catenin interactions, in vivo, leads to decreased postsynaptic accumulation of S-SCAM, but not PSD-93. Importantly, neuroligin synaptic clusters are also decreased. On the presynaptic side, there are decreases in neurexin and active zone proteins. Further, presynaptic terminals are less mature structurally and functionally. We define a novel neural role for APC by showing that the postsynaptic APC multiprotein complex is required for anchoring neuroligin and neurexin at neuronal synapses in vivo. APC human gene mutations correlate with autism spectrum disorders, providing strong support for the importance of the association, demonstrated here, between APC, neuroligin and neurexin. ER -