Researchers discover possible key to degenerative nerve diseases
Fruit fly eye.
(Medical Xpress) -- Researchers at the University of Wisconsin-Madison and collaborators have discovered a powerful new protein in the eye of the fruit fly that may shed light on blinding diseases and other sensory problems in humans.
Reporting in the Nov. 16, 2011, issue of Neuron, the scientists note that similar but yet- to-be-identified proteins in the eye and brain could help explain age-related macular degeneration and retinitis pigmentosa, as well as Huntington's, Parkinson's, Alzheimer's and prion diseases.
The protein, which the scientists have named XPORT, serves as a molecular chaperone for two important proteins that are key to sensory activities in the eye. One protein, rhodopsin, is responsible for absorbing light, and the other protein, TRP, is a channel that plays a role in calcium influx into cells. XPORT guides the two proteins from the place where they are made in the cell to the location where they do their jobs.
This intricate process of chaperoning includes synthesis, folding, assembly, quality control, transport and targeting of proteins to their appropriate locations, explains senior author Dr. Nansi Jo Colley of the UW School of Medicine and Public Health. The complex process is prone to error, and a malfunction in any of the steps can have dire consequences in tissues.
"Accumulation of misfolded proteins often leads to severe pathology and cell death, producing blinding diseases and other neurodegenerative diseases," says Colley, a professor in the Department of Ophthalmology and Visual Sciences, the Department of Genetics and the Eye Research Institute. "Molecular chaperones are one of the first lines of defense in these fundamental processes."
Colley and her team discovered XPORT as a result of screening a collection of 900 fruit-fly mutants that undergo retinal degeneration. The XPORT mutant displayed retinal degeneration and defects in rhodopsin and TRP.
"TRP channels play a vital role as biological sensors, regulating calcium entering cells involved in vision, taste, olfaction, hearing and touch," says Colley, adding that the channels are found in many organisms and tissues. "Defective TRP channels can cause night blindness in certain people."
The first author on the paper, Erica Rosenbaum, a doctoral student in the UW Neuroscience Training Program where Colley is a faculty member, joined with Colley and UW collaborators Kimberly S. Brehm and Eva Vasilijevic, as well as Che-Hsiung Liu and Roger C. Hardie at Cambridge University. Together they identified the mutation and discovered a small novel gene never described before.
They named the protein XPORT, for exit protein of rhodopsin and TRP.
In their experiments, the scientists showed that XPORT forms a complex with rhodopsin and TRP, and is required to successfully transport the two proteins to a specific location on the cell surface. They also determined that XPORT is essential for cell survival-mutations in XPORT prevented the two proteins from moving through the trafficking pathway, and this ended in retinal degeneration and blindness in the fly.
XPORT was also found to interact closely with another family of molecular chaperones called heat shock proteins, which are indispensable in the folding of newly synthesized proteins.
"Heat shock proteins have also been implicated as agents that protect nerve cells from degeneration," Colley says, "so XPORT or XPORT-like proteins might have therapeutic potential as well."
While XPORT is an eye-specific protein that is expressed in flies and other insects, Colley expects that a protein very similar to XPORT exists in humans.
The lab works on fruit flies because, as Colley says, "It is an invaluable model system for unraveling the complexity of many neurodegenerative diseases stemming from protein misfolding and aggregation. Studies using molecular genetics in the fruit fly are already greatly improving our ability to treat and perhaps even prevent these diseases."
Provided by University of Wisconsin-Madison
- Light-sensing receptor plays role in temperature sensation: study Mar 10, 2011 | not rated yet | 0
- Researchers discover key to cell specialization Nov 10, 2011 | not rated yet | 0
- Blame the 'chaperone' Jan 07, 2011 | not rated yet | 0
- All eyes on retinal degeneration Feb 16, 2010 | not rated yet | 0
- New study uncovers how brain cells degrade dangerous protein aggregates Nov 07, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
23 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
Neuroscience 10 hours ago | 4.8 / 5 (5) | 0 |
(Medical Xpress)—The human brain is able to identify individuals' voices by comparing them against an internal 'average voice' prototype, according to neuroscientists.
Neuroscience 14 hours ago | 1 / 5 (1) | 0 |
A new study determined that children and adolescents with seizures involving the temporal lobe are likely to have clinically significant behavioral problems and psychiatric illness, especially depression. Findings published ...
Neuroscience 14 hours ago | not rated yet | 0
As the human body fine-tunes its neurological wiring, nerve cells often must fix a faulty connection by amputating an axon—the "business end" of the neuron that sends electrical impulses to tissues or other ...
Neuroscience 16 hours ago | 5 / 5 (2) | 0 |
A study by researchers at Henry Ford Hospital found "substantial evidence" that a regenerative process involving damaged nerve fibers in the spinal cord could hold the key to better functional recovery by most stroke victims.
Neuroscience 16 hours ago | not rated yet | 0 |
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
15 hours ago | 4.5 / 5 (10) | 1 |
Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.
13 hours ago | 5 / 5 (1) | 2 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
13 hours ago | 5 / 5 (2) | 0 |
Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center ...
14 hours ago | not rated yet | 0 |
Ethnic background plays a surprisingly large role in how diabetes develops on a cellular level, according to two new studies led by researchers at the Stanford University School of Medicine.
11 hours ago | not rated yet | 0 |
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
12 hours ago | not rated yet | 0 |