Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex

Mol Cell Neurosci. 2008 Jun;38(2):138-52. doi: 10.1016/j.mcn.2008.02.006. Epub 2008 Mar 4.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Animals
  • Cells, Cultured
  • Chick Embryo
  • Chickens
  • Cytoskeleton / metabolism*
  • Electrophysiology
  • Endocytosis / physiology
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Ganglia, Parasympathetic / cytology
  • Gene Transfer Techniques
  • Membrane Potentials / physiology
  • Neurons / cytology
  • Neurons / physiology*
  • Receptors, Glycine / genetics
  • Receptors, Glycine / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Synapses / metabolism*
  • alpha7 Nicotinic Acetylcholine Receptor


  • 14-3-3 Proteins
  • Adenomatous Polyposis Coli Protein
  • Receptors, Glycine
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • nicotinic receptor subunit alpha3