Tufts University LogoA minute intercellular junction is believed to transfer information from one neuron to the next repeatedly. However, the synapse seemingly reveals more secrets and can provide a clue that triggers autism and mental retardation. Neuroscientists at Tufts University School of Medicine affirm that the protein adenomatous polyposis coli (APC) is a hallmark in synapse maturation, and it restricts the synapse function essential for typical learning and memory.

At the time of the in vivo study, investigators blocked APC function and observed that synaptic levels of the cell adhesion proteins neuroligin and neurexin significantly lowered. In the absence of normal protein levels, synapses were seemingly less mature not only structurally but also functionally. In humans, scientists have for long linked mutations in the genes for neuroligin and neurexin. But the mechanisms involved in localizing these proteins at the synapse were apparently unknown.

Michele H. Jacob, PhD, professor in the department of neuroscience at Tufts University School of Medicine and the senior author, added, “Both sides of the synapse are finely tuned for efficient transmission; an imbalance on either side can negatively impact function, resulting in cognitive deficits. Our study reveals that APC forms a key protein complex in the postsynaptic neuron that also provides signals to direct synapse maturation in the presynaptic neuron, ensuring that the two sides of the synapse mature in concert to provide optimal function.”

The investigators have also elucidated the process probably occurring between presynaptic and postsynaptic neurons. After interfering with APC function on the postsynaptic side, researchers observed changes on both sides of the synapse. These alterations may be indicating the fact that APC organizes a protein complex communicating against the normal flow of traffic.

Jacob highlighted, “Our laboratory study is the first to show that APC is needed to recruit neuroligin and neurexin to the synapse. This finding provides new insights into the mechanisms required for proper synapse function as well as molecular changes at the synapse that likely contribute to autistic behaviors and learning deficits in people with APC loss of function gene mutations.”

The research highlights the probable association between APC protein to autism and mental retardation. Further investigations will be undertaken to analyze the behavioral and cognitive alterations taking place when APC is removed in neurons of the mammalian brain. A new mouse model has been created for investigating the way loss of APC function leads to synaptic changes and impaired learning and memory.

The research was published in the August 18 issue of The Journal of Neuroscience.