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."
"A single nerve cell synthesizes multiple different neurotransmitter receptor types. The nerve cell must target each of them to distinct synaptic sites that oppose incoming nerve cell contacts that release the correct transmitter to activate that receptor type. Matching of receptor and transmitter types is critical for proper function," states Madelaine Rosenberg, PhD, first author and research associate in the department of neuroscience at TUSM. Rosenberg says that APC and its associated proteins play a key role in accomplishing this task at cholinergic synapses. The authors report that APC interacts with and positions the microtubule plus-end binding protein EB1 and thereby directs the delivery of acetylcholine receptors to restricted surface membrane regions. APC and EB1 interact with other proteins, cytoskeletal regulators and adapter proteins, which together stabilize the scaffold at the synapse and link acetylcholine receptors to APC at the complex. This study identifies several novel components of neuronal nicotinic cholinergic synapses.
Jacob and colleagues showed that blocking APC function led to dramatic and specific decreases in acetylcholine receptor levels at synapses. They showed this by using molecular techniques to manipulate APC protein interactions during synapse formation. "We study an in vivo model system to gain insights into mechanisms that likely direct synapse assembly and function in the human nervous system," Jacob explains. She further suggests that their data "support the emerging concept that APC is a central organizer of a core multi-protein complex that directs the assembly of excitatory, but not inhibitory, synapses in the vertebrate nervous system. The importance of APC's neural role is highlighted by reports that loss of function gene mutations correlate with mental retardation, schizophrenia, and autism spectrum disorders." Jacob notes, "By identifying the synapse organizing role of APC and its associated proteins, our findings bring us closer to understanding disorders of cognition and neurological function on a molecular level."
This study is funded by the National Institute of Neurological Disorders and Stroke (NINDS) through grants to Dr. Jacob and the Tufts Center for Neuroscience Research, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) through Tufts Medical Center Digestive Disease Center. Both NINDS and NIDDK are part of the National Institutes of Health.
Rosenberg MM, Yang F, Giovanni M, Mohn J, Temburni MK, Jacob M. Molecular and Cellular Neuroscience. 2008 (June);38(2):138-152."Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex." Published online March 4, 2008, doi:10.1016/j.mcn.2008.02.006
About Tufts University School of Medicine
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, 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. The Sackler School undertakes research that is consistently rated among the highest in the nation for its impact 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 Andrea Grossman at 617-636-3728.
Christine Fennelly | EurekAlert!
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Earth Sciences
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy