Featured Research

from universities, journals, and other organizations

Barriers, molecular trains trap Joubert syndrome protein in cilia

Date:
December 5, 2013
Source:
UCD Conway Institute of Biomolecular & Biomedical Research
Summary:
A cilia disease protein causing Joubert Syndrome, ARL-13, is actively trafficked across the base of cilia and molecular diffusion barriers prevent its exit, according to new research. Primary cilia are hair-like projections extending from the surfaces of most human cell types that serve as important antennae to relay external sensory and signalling information back to the cell. Disrupting cilium structure or function leads to a wide range of diseases, termed ciliopathies, linked to multiple symptoms including cystic kidneys, blindness, bone formation defects, mental retardation and obesity.

A cilia disease protein causing Joubert Syndrome, ARL-13, is actively trafficked across the base of cilia and molecular diffusion barriers prevent its exit, according to new research from the UCD Conway Institute published today in PLoS Genetics.

Related Articles


Primary cilia are hair-like projections extending from the surfaces of most human cell types that serve as important antennae to relay external sensory and signalling information back to the cell. Disrupting cilium structure or function leads to a wide range of diseases, termed ciliopathies, linked to multiple symptoms including cystic kidneys, blindness, bone formation defects, mental retardation and obesity.

An important feature of the cilium is its compartmentalised nature. This allows many proteins, including those involved in ciliopathies to become specifically enriched within the structure where they function. Although not well understood, the process of ciliary compartmentalisation is thought to involve active transport systems such as intraflagellar transport (IFT) and molecular diffusion barriers at the ciliary base (transition zone).

Using a combination of genetics and live imaging approaches, Dr Oliver Blacque and his team in the UCD Conway Institute have recorded the movement of molecules across the base of cilia in real-time, which provided kinetic information about the barrier itself. They believe this is the first time fluorescent recovery after photobleaching (FRAP) has been used in an 'in vivo' setting to assess protein diffusion into and out of cilia.

The team showed that proteins causing Meckel syndrome and nephronophthisis, which are symptomatically related to Joubert syndrome, comprise a barrier at the transition zone that prevents leakage of ciliary membrane-associated ARL-13 out of cilia. In contrast, they found that IFT proteins play no role in barrier formation but instead are required for actively transporting ARL-13 across the barrier.

Commenting on the significance of the research, Dr Blacque said, "We have been able to directly test 'in vivo' the interplay of active transport and membrane diffusion barrier mechanisms in restricting proteins to cilia. We found that Joubert syndrome-associated ARL-13 can act as a cargo of intraflagellar transport (IFT) trains as they move from the periciliary membrane into the cilium, across a transition zone barrier directly regulated by MKS and NPHP (cilia disease) proteins.

These findings extend our previous work that suggested a diffusion barrier at the ciliary base, and again show how nematode genetics and imaging serve as powerful allies for uncovering basic principles of cell biology and human disease gene pathomechanisms."

The Blacque team, who led the entire study, worked in conjunction with the UCD Conway Imaging Core facility to develop the FRAP technique. They also collaborated with colleagues in the Universities of Radboud and Tuebingen to identify the composition of human Arl13b complexes using semi-quantitative and quantitative (SILAC) affinity proteomics.

Dr Blacque and his team now hope to use their FRAP assay to uncover more genes directly responsible for establishing diffusion barriers at the ciliary base and define their precise kinetic contributions to barrier function.

At a wider level, this work will help to shed light on how important signalling processes are confined to small regions of the cell's plasma membrane.


Story Source:

The above story is based on materials provided by UCD Conway Institute of Biomolecular & Biomedical Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Oliver E. Blacque et al. Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain. PLoS Genetics, December 2013

Cite This Page:

UCD Conway Institute of Biomolecular & Biomedical Research. "Barriers, molecular trains trap Joubert syndrome protein in cilia." ScienceDaily. ScienceDaily, 5 December 2013. <www.sciencedaily.com/releases/2013/12/131205185522.htm>.
UCD Conway Institute of Biomolecular & Biomedical Research. (2013, December 5). Barriers, molecular trains trap Joubert syndrome protein in cilia. ScienceDaily. Retrieved January 26, 2015 from www.sciencedaily.com/releases/2013/12/131205185522.htm
UCD Conway Institute of Biomolecular & Biomedical Research. "Barriers, molecular trains trap Joubert syndrome protein in cilia." ScienceDaily. www.sciencedaily.com/releases/2013/12/131205185522.htm (accessed January 26, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, January 26, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Water Fleas Prepare for Space Voyage

Water Fleas Prepare for Space Voyage

Reuters - Innovations Video Online (Jan. 26, 2015) Scientists are preparing a group of water fleas for a unique voyage into space. The aquatic crustaceans, known as Daphnia, can be used as a miniature model for biomedical research, and their reproductive and swimming behaviour will be tested for signs of stress while on board the International Space Station. Jim Drury went to meet the team. Video provided by Reuters
Powered by NewsLook.com
Florida Might Legalize Black Bear Hunting

Florida Might Legalize Black Bear Hunting

Newsy (Jan. 24, 2015) A string of black bear attacks has Florida officials considering lifting the ban on hunting the animals to control their population. Video provided by Newsy
Powered by NewsLook.com
Ebola Killing Large Portion Of Ape Population

Ebola Killing Large Portion Of Ape Population

Newsy (Jan. 23, 2015) Experts estimate Ebola has wiped out one-third of the world&apos;s gorillas and chimpanzees. Video provided by Newsy
Powered by NewsLook.com
Controversy Shrouds Captive Killer Whale in Miami

Controversy Shrouds Captive Killer Whale in Miami

Reuters - Light News Video Online (Jan. 23, 2015) Activists hope the National Oceanic and Atmospheric Agency (NOAA) will label killer whales endangered, allowing lawyers to sue a Miami aquarium to release an orca into the wild after 44 years. Jillian Kitchener reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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