Rapid information processing in the nervous system requires synapses, specialized contact sites between nerve cells and their targets. One particular synapse type, cholinergic, uses the chemical transmitter acetylcholine to communicate between nerve cells. Cholinergic synapses are essential for normal learning and memory, arousal, attention, and all autonomic (involuntary) nervous system functions.
Malfunction of cholinergic synapses is implicated in Alzheimer's disease, age-related hearing loss, autonomic neuropathies, and certain forms of epilepsy and schizophrenia. Despite the importance of cholinergic synapses for cognitive and autonomic functions, little is known about the mechanisms that direct their assembly during development. In a new study published in the June 2008 issue of Molecular and Cellular Neuroscience, researchers at Tufts University School of Medicine (TUSM), uncover mechanisms that direct cholinergic synapse assembly between neurons in vivo.
"We have identified the protein adenomatous polyposis coli (APC) as a key organizer of a multi-protein complex that is required for assembly of neuronal cholinergic synapses" says corresponding author Michele H. Jacob, PhD, professor of neuroscience at TUSM and member of the neuroscience program faculty of the Sackler School of Graduate Biomedical Sciences. "APC is expressed in all cell types and has multiple functions and binding partners. It is best known for its role in colorectal cancer. Our work defines a novel role for APC in neurons. We show that APC brings together several proteins at the synapse and coordinates their functions in directing the surface membrane delivery and stable retention of nicotinic acetylcholine receptors at the synapse."