title: Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex.
abstract: The neuronal nicotinic synapse plays a central role in normal cognitive and autonomic function. Molecular mechanisms that direct the assembly of this synapse remain poorly defined, however. We show here that adenomatous polyposis coli (APC) organizes a multi-molecular complex that is essential for targeting alpha3(*)nAChRs to synapses. APC interaction with microtubule plus-end binding protein EB1 is required for alpha3(*)nAChR surface membrane insertion and stabilization. APC brings together EB1, the key cytoskeletal regulators macrophin and IQGAP1, and 14-3-3 adapter protein at nicotinic synapses. 14-3-3, in turn, links the alpha3-subunit to APC. This multi-molecular APC complex stabilizes the local microtubule and F-actin cytoskeleton and links postsynaptic components to the cytoskeleton--essential functions for controlling the molecular composition and stability of synapses. This work identifies macrophin, IQGAP1 and 14-3-3 as novel nicotinic synapse components and defines a new role for APC as an in vivo coordinator of nicotinic postsynaptic assembly in vertebrate neurons.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA.
authors.forename: Madelaine M
authors.initials: MM
authors.lastname: Rosenberg
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Monica
authors.initials: M
authors.lastname: Giovanni
authors.forename: Jesse L
authors.initials: JL
authors.lastname: Mohn
authors.forename: Murali K
authors.initials: MK
authors.lastname: Temburni
authors.forename: Michele H
authors.initials: MH
authors.lastname: Jacob
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D003599:Cytoskeleton / Q000378:metabolism*; D004594:Electrophysiology; D004705:Endocytosis / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005726:Ganglia, Parasympathetic / Q000166:cytology; D018014:Gene Transfer Techniques; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D048948:14-3-3 Proteins; D025601:Adenomatous Polyposis Coli Protein; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor