Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 38, Issue 2, Pages 138-152Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.02.006
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Funding
- NIDDK NIH HHS [P30 DK34928, P30 DK034928] Funding Source: Medline
- NINDS NIH HHS [P30 NS047243, NS21725, R01 NS021725-23, R01 NS021725] Funding Source: Medline
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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 alpha 3*nAChRs to synapses. APC interaction with microtubule plus-end binding protein EB1 is required for alpha 3*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 alpha 3-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. (C) 2008 Elsevier Inc. All rights reserved.
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