Researchers Reveal Structure of Protein Altered in Autism
June 12, 2007
Neuroligin/neurexin complex in the synapse.
As a result of mapping the structure of the protein complex implicated in autism spectrum disorders, a research team led by scientists at the University of California, San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences has discovered how particular genetic mutations affect this complex and contribute to the developmental abnormalities found in children with autism. Their work, published as the cover article in the June issue of the journal Structure, should help scientists pinpoint the consequences of other genetic abnormalities associated with the disorder.
“By understanding the three-dimensional structure of the normal protein, researchers can now make predictions about how mutations in the gene affect the structure of the gene product,” said first author Davide Comoletti, Ph.D., UCSD research associate at the Skaggs School of Pharmacy.
Autism spectrum disorders are developmental disabilities that cause impairments in social interaction and communication. Both children and adults with autism typically show difficulties in verbal and non-verbal communication, interpersonal relationships, and leisure or play activities.
Comoletti and colleagues studied the neuroligin family of proteins that are encoded by genes known to be mutated in certain patients with autism. The neuroligins, and their partner proteins, the neurexins, are involved in the junctions, or synapses, through which cells of the nervous system signal to one another and to non-neuronal tissues such as muscle. These structural studies on neuroligins and neurexins represent a major step toward defining the synaptic organization at the molecular level.
“Normally, individual neuroligins are encoded to interact with specific neurexin partners. The two partners are members of distinct families of proteins involved in synaptic adhesions, imparting ‘stickiness’ that enables them to associate so that synapses form and have the capacity for neurotransmission,” said Palmer Taylor, Ph.D., Dean of the Skaggs School, Sandra & Monroe Trout Professor of Pharmacology, and co-principal investigator of the study, along with Jill Trewhella, Ph.D., of the University of Sydney, Australia and University of Utah.
Incorrect partnering that results when a mutant neuroligin fails to properly align at synapses helps explain why the autism spectrum disorders are manifested in subtle behavioral abnormalities that are seen at an early age.
“Abnormal synaptic development in nerve connections is likely to lead to cognitive deficits seen in patients with autism,” said Taylor. He added that synapse formation and maintenance occurs early in development when the infant brain is still plastic and formative. Therefore, by understanding the structural mutations that affect neurotransmission during development, new leads into drug therapies may emerge.
“We really don’t know what causes autism, but this research represents a solid starting point,” said Sarah Dunsmore, Ph.D., program director with the National Institute of General Medical Sciences, part of the National Institutes of Health, which partly supported the study. “The work suggests that genetic mutations that alter the shape or folding of adhesion proteins in the nervous system influence their interactions. This is another example of how research on basic biological questions, such as the three-dimensional structures of proteins in the brain, can yield valuable medical insights.”
Taylor and colleagues have been studying the structure and function of acetylcholinesterase – a structurally related protein that mediates neurotransmission between nerves and between nerve and muscle – for the past 30 years. They began studying the neuroligins because of the similarity in structure and amino acid sequence with acetylcholinesterase.
Source: University of California - San Diego
-
Gene mutation in autism found to cause hyperconnectivity in brain's hearing center
Jan 31, 2012 |
5 / 5 (2) |
0
-
Evolved, mutated gene module linked to Joubert syndrome
Jan 26, 2012 |
5 / 5 (3) |
0
-
New automated imaging to greatly speed whole-brain mapping efforts
Jan 15, 2012 |
4.3 / 5 (14) |
3
-
Hold that thought? Scientists find sensor that may explain working memory
Dec 21, 2011 |
4.7 / 5 (7) |
1
-
Neurons grown from skin cells may hold clues to autism
Nov 27, 2011 |
4.5 / 5 (4) |
1
-
Engineers build first sub-10-nm carbon nanotube transistor
Feb 01, 2012 |
4.9 / 5 (33) |
30
-
Something old, something new: Evolution and the structural divergence of duplicate genes
Jan 31, 2012 |
4.6 / 5 (7) |
1
-
The hidden nanoworld of ice crystals: Revealing the dynamic behavior of quasi-liquid layers
Jan 30, 2012 |
5 / 5 (4) |
1
-
Stock market network reveals investor clustering
Jan 27, 2012 |
3.9 / 5 (23) |
8
-
Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes
Jan 26, 2012 |
5 / 5 (2) |
0
-
Is Everyday Technology Killing Us?
Feb 08, 2012
-
Exercise and weight loss
Feb 08, 2012
-
Why do we have head aches? Our brains can't feel anything.
Feb 07, 2012
-
"The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
Feb 04, 2012
-
Oncolytic adenovirus
Feb 04, 2012
-
Nutrition label stuffs and diets
Feb 02, 2012
- More from Physics Forums - Medical Sciences
More news stories
Overeating may double risk of memory loss
New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study was released today and will be ...
Medicine & Health / Neuroscience
1 hour ago |
5 / 5 (1) |
0
|
Injured boomers beware: Know when to see doctor
(AP) -- It happened to nurse Jane Byron years after an in-line skating fall, business owner Haralee Weintraub while doing "men's" push-ups, and avid cyclist Gene Wilberg while lifting a heavy box.
6 hours ago |
5 / 5 (1) |
0
Starve a virus, feed a cure? Findings show how some cells protect themselves against HIV
A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online ...
5 hours ago |
5 / 5 (1) |
0
|
FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice
Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...
Medicine & Health / Neuroscience
Feb 09, 2012 |
4.9 / 5 (58) |
15
|
Green tea found to reduce disability in the elderly
(Medical Xpress) -- A lot of research has been done over the past several years looking into the health benefits of green tea. As a result, scientists have found that regular consumption of the beverage leads ...
Google might launch Drive for cloud storage soon
(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...
Scientists discover molecular secrets of 2,000-year-old Chinese herbal remedy
For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, ...
New method to examine batteries -- MRI from the inside
There is an ever-increasing need for advanced batteries for portable electronics, such as phones, cameras, and music players, but also to power electric vehicles and to facilitate the distribution and storage of energy derived ...
Lab study raises questions over nano-particle impact
Tests involving chickens have raised questions about the impact on health from engineered nano-particles, the ultra-fine grains commonly used in drugs and processed foods, scientists said on Sunday.
A mitosis mystery solved: How chromosomes align perfectly in a dividing cell
Although the process of mitotic cell division has been studied intensely for more than 50 years, Whitehead Institute researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric ...
Researchers find extensive RNA editing in human transcriptome
In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demons ...