Featured Research

from universities, journals, and other organizations

Architecture of rod sensory cilium disrupted by mutation

Date:
November 21, 2012
Source:
Baylor College of Medicine
Summary:
Using a new technique called cryo-electron tomography, scientists have created a three-dimensional map that gives a better understanding of how the architecture of the rod sensory cilium (part of one type of photoreceptor in the eye) is changed by genetic mutation and how that affects its ability to transport proteins as part of the light-sensing process.

Using a new technique called cryo-electron tomography, two research teams at Baylor College of Medicine have created a three-dimensional map that gives a better understanding of how the architecture of the rod sensory cilium (part of one type of photoreceptor in the eye) is changed by genetic mutation and how that affects its ability to transport proteins as part of the light-sensing process.

Almost all mammalian cells have cilia. Some are motile and some are not. They play a central role in cellular operations, and when they are defective because of genetic mutations, people can go blind, have cognitive defects, develop kidney disease, grow too many fingers or toes or become obese. Such mutations cause cilia defects known in the aggregate as ciliopathies.

Three-dimensional look

"The major significance of this report lies in our being able to, for the first time, look in three dimensions at the structural alterations in ciliopathies," said Dr. Theodore G. Wensel, chair of biochemistry and molecular biology at BCM and corresponding author of the report that appears in the journal Cell.

In collaboration with the National Center for Macromolecular Imaging, led by Dr. Wah Chiu, professor of biochemistry and molecular biology at BCM, Wensel and his colleagues established such three dimensional images for cilia in three examples of mice known to have cilopathies.

These mice have genetic mutations that lead to defects in the structure of the rod outer segment. The rod outer segment is part of the photoreceptor in the retina called a rod. The rod outer segment contains photosensitive disk membranes that carry rhodopsin, the biological pigment in photoreceptor cells of the retina responsible for the first events that result in the perception of light.

Comparing rod outer segments

Using cryo-electron tomography, the scientists compared the structures of the rod outer segment in the mutant mice to those in normal mice.

"This is one of the few places in the world where you could do this," said Wensel. The center, run by Chiu, has powerful cryo-electron microscopes that make tomography possible. To achieve the three-dimensional reconstruction, Dr. Juan T. Chang in Chiu's center froze the photoreceptors purified by then-graduate student Jared Gilliam in a special way that made it possible to perform electron microscopy. During the microscopy session, the frozen samples were carefully tilted allowing the researchers to take many two-dimensional images that were used in the computer reconstruction of the three-dimensional map.

The light-sensing outer segments of photoreceptors in the retina are connected to the machinery responsible for protein production in the inner segment by a thin cylindrical bundle of microtubules known as the connecting cilium.

"There is a huge flux of material from the inner segment to the outer segment of the photoreceptor," said Wensel. "When there is a defect, then the animal or patient goes blind."

The three-dimensional structure showed that there are vesicles (small sacs) tethered to membrane filaments.

"It looks as though these vesicles that are tethered contain material that will fuse to the plasma membrane and go up the membrane to the outer segment," said Wensel.

Photoreceptor degeneration

In studies of a mouse model of a disease called Bardet Biedl syndrome, developed by the laboratory of Dr. James Lupski, professor of molecular and human genetics at BCM, Wensel and first author Gilliam saw something that was almost shocking--a huge accumulation of these vesicles. The Bardet Biedl genes contain the code for a BBsome that forms a membrane coat that makes transport possible through the connecting cilium to the outer coat.

"We would now surmise that the BBsome coat is required for fusion of the plasma membrane or transport up to the outer segment," said Wensel. "It gives us a whole new model for how this works. We need to do more now to nail it down."

"It suggests that aberrant trafficking of proteins is responsible for photoreceptor degeneration," said Gilliam, who is now a postdoctoral associate at The University of Texas Health Science Center at Houston.

Others who took part in the research include: BCM graduate student Ivette Sandoval; Youwen Zhang and Steven J. Pittler, both of the University of Alabama at Birmingham; and Tiansen Li of the National Eye Institute in Bethesda, Maryland.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. JaredC. Gilliam, JuanT. Chang, IvetteM. Sandoval, Youwen Zhang, Tiansen Li, StevenJ. Pittler, Wah Chiu, TheodoreG. Wensel. Three-Dimensional Architecture of the Rod Sensory Cilium and Its Disruption in Retinal Neurodegeneration. Cell, 2012; 151 (5): 1029 DOI: 10.1016/j.cell.2012.10.038

Cite This Page:

Baylor College of Medicine. "Architecture of rod sensory cilium disrupted by mutation." ScienceDaily. ScienceDaily, 21 November 2012. <www.sciencedaily.com/releases/2012/11/121121145621.htm>.
Baylor College of Medicine. (2012, November 21). Architecture of rod sensory cilium disrupted by mutation. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/11/121121145621.htm
Baylor College of Medicine. "Architecture of rod sensory cilium disrupted by mutation." ScienceDaily. www.sciencedaily.com/releases/2012/11/121121145621.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins