According to neuroscientists at Tufts University School of Medicine, with students from the Sackler School of Graduate Biomedical Sciences at Tufts, a protein called APC (adenomatous polyposis coli) plays a key role in synapse maturation, and APC dysfunction prevents the synapse function required for typical learning and memory. The findings are published in the August 18 issue of The Journal of Neuroscience.
“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,” said senior author Michele H. Jacob, PhD, professor in the department of neuroscience at Tufts University School of Medicine. Jacob is also a member of the cell, molecular and developmental biology; cellular and molecular physiology; and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.
In the in vivo study, the team blocked APC function and found that synaptic levels of the cell adhesion proteins neuroligin and neurexin dropped considerably. Without normal levels of these proteins, synapses were less mature both structurally and functionally. Mutations in the genes for neuroligin and neurexin are associated with autism in humans, but until now, little was known about the mechanisms responsible for localizing these proteins at the synapse. “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,” said Jacob.
“Our study also sheds light on a poorly-understood but essential process, the cross-talk that occurs between presynaptic and postsynaptic neurons. 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,” said first author Madelaine Rosenberg, PhD, an affiliate of the department of neuroscience at TUSM.
The research team’s next step is to examine the behavioral and cognitive changes that occur when APC is deleted in neurons of the mammalian brain. They have developed a new mouse model that will allow them to investigate how the loss of APC function leads to synaptic changes and impaired learning and memory.
Additional authors are Fang Yang, PhD, a research associate in the department of medicine at TUSM; Jesse Mohn, a PhD candidate in the cell, molecular, and developmental biology program at Sackler and member of Jacob’s lab; and Elizabeth Storer, a PhD candidate in the neuroscience program at Sackler and member of Jacob’s lab.
This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, and the Tufts Center for Neuroscience Research. The Tufts Center for Neuroscience Research, itself, is supported by NINDS and by Tufts University School of Medicine and Tufts Medical Center.
Rosenberg MM, Yang F, Mohn JL, Storer EK, Jacob MH. The Journal of Neuroscience. 2010. (August 18); 30(33): 11073-11085. “The Postsynaptic Adenomatous Polyposis Coli (APC) Multiprotein Complex Is Required for Localizing Neuroligin and Neurexin to Neuronal Nicotinic Synapses in Vivo.” Published online August 18, 2010, doi: 10.1523/JNEUROSCI.0983-10.2010
About Tufts University School of Medicine and the SacklerSchool of Graduate Biomedical Sciences
TuftsUniversitySchool of Medicine and the Sackler School of Graduate Biomedical Sciences at TuftsUniversity are international leaders in innovative medical education and advanced research. The School of Medicine and the SacklerSchool are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. TuftsUniversitySchool of Medicine and the SacklerSchool undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.
If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences, or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.
Siobhan Gallagher | EurekAlert!
First line of defence against influenza further decoded
21.02.2018 | Helmholtz-Zentrum für Infektionsforschung
Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates
21.02.2018 | Institute of Science and Technology Austria
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Earth Sciences
21.02.2018 | Health and Medicine
21.02.2018 | Life Sciences