Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Researchers Get Close-Up View of Water Pores Needed in the Eye's Lens

Published: Tuesday, August 06, 2013
Last Updated: Tuesday, August 06, 2013
Bookmark and Share
NIH-funded study of aquaporins could hold clues to cataract.

Researchers have achieved dynamic, atomic-scale views of a protein needed to maintain the transparency of the lens in the human eye.

The work, funded in part by the National Institutes of Health, could lead to new insights and drugs for treating cataract and a variety of other health conditions.

Aquaporin proteins form water channels between cells and are found in many tissues, but aquaporin zero (AQP0) is found only in the mammalian lens, which focuses light onto the retina, at the back of the eye.

The lens is primarily made up of unique cells called lens fibers that contain little else besides water and proteins called crystallins.

Tight packing of these fibers and of the crystallin proteins within them helps create a uniform medium that allows light to pass through the lens, almost as if it were glass.

Abnormal development or age-related changes in the lens can lead to cataract - a clouding of the lens that causes vision loss.

Besides age, other risk factors for cataract include smoking, diabetes, and genetic factors. Mutations in the AQP0 gene can cause congenital cataract and may increase the risk of age-related cataract.

"The AQP0 channel is believed to play a vital role in maintaining the transparency of the lens and in regulating water volume in the lens fibers, so understanding the molecular details of how water flows through the channel could lead to a better understanding of cataract," said Dr. Houmam Araj, who oversees programs on lens, cataract and oculomotor systems at NIH's National Eye Institute (NEI), which helped fund the research.

Closing of AQP0 channels is regulated by a calcium-sensitive protein called calmodulin, but the precise mechanism has been unclear.

Some models have suggested that calmodulin simply acts as a plug to fill the open channel. The new study, published in Nature Structural and Molecular Biology, reveals a more nuanced process in which calmodulin essentially grasps the open channel and forces it to close.

The research was a collaboration between investigators at the University of California, Irvine, and the Janelia Farm Research Campus in Ashburn, Va., a part of the Howard Hughes Medical Institute (HHMI).

Drs. James Hall and Douglas Tobias led the effort at UC Irvine. Dr. Tamir Gonen led the effort at Janelia Farm.

In prior studies, Dr. Gonen had examined the atomic structure of the AQP0 protein by X-ray crystallography, which involves crystallizing a protein and bombarding it with X-rays. But X-ray crystallography does not work well for large groups of proteins or for proteins in motion.

So in the new study, the researchers first used electron microscopy to view AQP0 and calmodulin bound together. Then they combined their microscopy and crystallography data to generate computerized models of how the two proteins interact and to identify the most critical amino acids (the building blocks for proteins) within AQP0.

To test their models, they neutralized those amino acids one by one in the actual AQP0 channel.

The AQP0 channel is made up of four identical barrel-shaped units, bundled together side by side. The researchers found that in the presence of calcium, calmodulin binds to one unit and then another, as if grabbing a pair of reins.

This makes the channel twist slightly, which causes just a few amino acids within each unit to slide into the channel's core and block the flow of water.

"Calmodulin essentially throws a molecular switch that moves in and out of the water pore, like the gate valve of a plumbing fixture," Dr. Hall said.

This new view of AQP0 could help lead to new approaches for treating cataract, Dr. Hall said. Cataracts are the most common cause of blindness worldwide.

In the United States, they affect about 1 in 6 people over age 40 and half over age 80. Congenital cataracts (present from birth) affect about 1 in 5,000 American children.

Cataracts can be successfully treated with surgery, in which the cloudy lens is removed and replaced with an artificial plastic lens. But the new findings "may be a step toward learning how to prevent or delay cataracts," said Dr. Hall.

The new findings also provide inroads to understanding how calmodulin interacts with a variety of protein channels, and thus could open doors to new drugs for other common health conditions.

In addition to aquaporins, our bodies rely on a vast menagerie of channels, many of which are regulated by calmodulin.

For example, calmodulin helps control the gating of ion channels, which allow the passage of ions (charged particles) in and out of our cells and are essential for nerve cell firing, muscle contraction, and the rhythmic beating of the heart. This study provides the first structural model of calmodulin bound to any complete protein channel.

Drs. Daniel Clemens and Steve Reichow were co-first authors on the study. NIH support for the study came from NEI (grants EY005661, EY018768), the National Institute of General Medical Sciences (NIGMS grant GM079233), a joint program on "Making Sense of Voltage Sensors" co-funded by NIGMS and the National Institute of Neurological Disorders and Stroke (grant GM086685), and the National Library of Medicine (grant LM007443).

Additional support came from HHMI, the National Science Foundation, and the German Academy of Sciences.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More Than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Friday, February 05, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
Monday, February 01, 2016
Schizophrenia’s Strongest Known Genetic Risk Deconstructed
Suspect gene may trigger runaway synaptic pruning during adolescence – NIH-funded study.
Thursday, January 28, 2016
Experimental Combination Surprises with Anti-HIV Effectiveness
A compound developed to protect the nervous system from HIV surprised researchers by augmenting the effectiveness of an investigational antiretroviral drug beyond anything expected.
Monday, January 25, 2016
Dengue Vaccine Enters Phase 3 Trial
Investigational vaccine to prevent ‘breakbone fever’ developed at NIH.
Friday, January 15, 2016
NIH Genome Sequencing Program Targets the Genomic Bases of Common, Rare Disease
The National Institutes of Health will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases.
Friday, January 15, 2016
Trying to Conceive Soon After a Pregnancy Loss May Increase Chances of Live Birth
NIH study finds no reason for delaying pregnancy attempts after a loss without complications.
Wednesday, January 13, 2016
Three Glaucoma-Related Genes Discovered
NIH-funded genetics analysis of glaucoma is largest to date.
Tuesday, January 12, 2016
NIH-funded Memory Drug Moves into Phase 1 Clinical Study
Collaboration between NIH and Tetra Discovery Partners leads to development of treatment that may affect cognition.
Monday, January 04, 2016
International Study Reveals New Genetic Clues to AMD
NIH-funded research provides framework for future studies of AMD biology, therapy.
Tuesday, December 22, 2015
NIH Unveils FY2016–2020 Strategic Plan
Detailed plan sets course for advancing scientific discoveries and human health.
Thursday, December 17, 2015
Biomarkers Outperform Symptoms in Parsing Psychosis Subgroups
Multiple biological pathways lead to similar symptoms - NIH-funded study.
Thursday, December 10, 2015
Researchers Investigate How a Developing Brain is Assembled
NIH 3-D software tracks worm embryo's brain development.
Tuesday, December 08, 2015
NIH Supports New Studies to Find Alzheimer’s Biomarkers in Down Syndrome
Initiative will track dementia onset, progress in Down syndrome volunteers.
Tuesday, December 01, 2015
Scientific News
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Genetic Cause of Rare Allergy
Institute has identified a genetic mutation responsible for a rare form of inherited hives induced by vibratory urticaria.
Battery Component Found to Harm Key Soil Microorganism
The material at the heart of the lithium ion batteries that power electric vehicles, laptop computers and smartphones has been shown to impair a key soil bacterium, according to new research.
Keeping Tumor Growth at Bay
Engineers at Washington University in St. Louis found a way to keep a cancerous tumor from growing by using nanoparticles of the main ingredient in common antacid tablets.
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Mitochondria Shown to Trigger Cell Ageing
An international team of scientists has for the first time shown that mitochondria, the batteries of the cells, are essential for ageing.
Cancer Cells Kill Off Healthy Neighbours
Cancer cells create space to grow by killing off surrounding healthy cells, according to UK researchers working with fruit flies.
Validating the Accuracy of CRISPR-Cas9
IBS Researchers create multiplex Digenome-seq to find errors in CRISPR-Cas9 processes.
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Genetic Mechanism Behind Cancer-Causing Mutations
Researchers at Indiana University has identified a genetic mechanism that is likely to drive mutations that can lead to cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!