APC Protein Connected to Autism and Mental Retardation
New findings are taking researchers and scientists one step closer to a better understanding of autism and mental retardation, the causes of which have long been the subject of intense study.
A study completed by neuroscientists at Tufts University School of Medicine (TUSM) and Sackler School of Graduate Biomedical Sciences at Tufts suggests that the causes of these disorders may rest with the dysfunction of a protein called adenomatous polyposis coli (APC), an important element that ffects the synapse’s ability to mature. A key player in the body’s nervous system, the synapse provides a gateway for neurons to quickly pass important signals to other cells and is essential for neurons to function properly.
According to senior author Michele H. Jacob, PhD, professor in the department of neuroscience at TUSM and faculty member with the Sackler School of Graduate Biomedical Sciences at Tufts, the study is the first to reveal that APC is required to bolster the production of neuroligin and neurexin in the synapse.
Neuroligin and neurexin are cell adhesion molecules required to properly mature the growth and functionality of the synapse gateway, specifically aiding with the transfer of signals across the synapse and determining synaptic functions.
“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,” Jacob said.
A neurodevelopmental disorder with a wide range of symptoms and severity, autism currently affects approximately one to two people per 1,000, and related disorders in the autism spectrum—Asperger’s disorder and pervasive development disorder (PPD)—are estimated to affect six in 1,000.
Autism and some forms of mental retardation have strong ties to genetics, and specifically, lack of APC protein will affect functions that aid with learning ability and memory, according to industry research. By blocking APC function, the research team was able to identify the drop in the neuroligin and neurexin proteins, ultimately revealing the connection between the two areas.
Jacobs added that “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.”
Mutations of the genes found in neuroligin and neurexin proteins have also been linked to autism, but past research did not identify the importance of APC in clustering these molecules in the synapse.
Madelaine Rosenberg, PhD, an affiliate of the department of neuroscience at TUSM and first author of the study noted that the study also provides a better understanding of the way presynaptic and postsynaptic neurons communicate. “When we perturbed APC function on the postsynaptic side, we saw changes on both sides of the synapse, indicating that APC organizes a protein complex that communicates against the normal flow of traffic,” she said.
To further the effort toward a better understanding of the causes of autism and mental retardation, the research team plans to study the effects of eliminating APC from a mammal’s brain.
Backers of the study include the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and the Tufts Center for Neuroscience Research.
The study’s findings are published in the August 18 issue of The Journal of Neuroscience.
Source: Tufts University
Chavis, S. (2010). APC Protein Connected to Autism and Mental Retardation. Psych Central. Retrieved on August 1, 2015, from http://psychcentral.com/news/2010/08/27/apc-protein-connected-to-autism-and-mental-retardation/17339.html