Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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

“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
Monday, September 26, 2016
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Public Support for National Study
Survey shows the majority of respondents support or show willingness for national precision medicine study.
Thursday, August 18, 2016
Schizophrenia, Autism Share Genetic Causes
Monkey brain developmental atlas pinpoints when, where genes activate.
Tuesday, August 16, 2016
How Breast Cancers Resist Chemotherapy
Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies.
Wednesday, August 10, 2016
Mutations Linked to Immunotherapy Resistance
Researchers uncover mutations in tumors of three patients with advanced melanoma that allowed the tumors to become resistant to the immune checkpoint inhibitor pembrolizumab (Keytruda®).
Tuesday, August 09, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Depression Genetics Insight from Crowd-Sourced Data
Genome sites liked to depression have been discovered from data shared by people who had purchased their genetic profiles online.
Tuesday, August 02, 2016
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Thursday, July 21, 2016
NIH Funds Million-Person Medicine Study
NIH announces $55million in awards to build foundations for ambitious Cohort Program that aims to engage 1 million participants in lifestyle, environments and genetics research.
Friday, July 08, 2016
Largest-Ever Study of Breast Cancer Genetics in Black Women
The study will identify genetic factors that may underlie breast cancer disparities.
Thursday, July 07, 2016
Significant Expansion Of Data Available In The Genomic Data Commons
Cancer genomic profile information from 18,000 adult cancer patients will be added to the database.
Wednesday, June 29, 2016
Scientific News
Blood Pressure Drug May Boost Effectiveness of Lung Cancer Treatment
Researchers at Imperial College London have suggested that the blood pressure drug may make a type of lung cancer treatment more effective.
Regulatory RNA Essential to DNA Damage Response
Researchers discover a tumour suppressor is stabilized by an RNA molecule, which helps cells respond to DNA damage.
Death-or-Repair Switch Protein Identified
Researchers have identified a protein that plays a key role in the decision process of cell damage repair or cellular suicide.
Heart Arrhythmia Caused by Mosaic of Mutant Cells
Researchers have solved the genetic mystery of an infant suffering from heart arrhythmia.
Crispr Toolbox Expanded By Protein
Researchers have shown a newly discovered CRISPR protein has two distinct RNA cutting activities.
Genetic Impact of Endurance Training
Research has found that endurance training changes genetic activity in thousands of genes, giving rise to large number of altered RNA variants.
Wearable Microscope Can Measure Fluorescent Dyes Through Skin
UCLA research could make monitoring disease biomarkers easier and more cost-effective.
“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
A Diversity of Genomes
New DNA from understudied groups reveals modern genetic variation, ancient population shifts.
Gene Could Reduce Female Mosquitoes
Virginia Tech researchers have found a gene that can reduce female mosquitoes over many generations.
Skyscraper Banner

SELECTBIO Market Reports
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!