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 April 23, 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 April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. 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