Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex.
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.
Rosenberg
Madelaine M
MM
Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA.
Yang
Fang
F
Giovanni
Monica
M
Mohn
Jesse L
JL
Temburni
Murali K
MK
Jacob
Michele H
MH
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
D048948:14-3-3 Proteins; D025601:Adenomatous Polyposis Coli Protein; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor