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.

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 July 24, 2014 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 July 24, 2014).

Share This




More Plants & Animals News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Dogs Appear To Become Jealous Of Owners' Attention

Dogs Appear To Become Jealous Of Owners' Attention

Newsy (July 23, 2014) A U.C. San Diego researcher says jealousy isn't just a human trait, and dogs aren't the best at sharing the attention of humans with other dogs. Video provided by Newsy
Powered by NewsLook.com
Professor Creates Site Revealing Where People's Cats Live

Professor Creates Site Revealing Where People's Cats Live

Newsy (July 23, 2014) ​It's called I Know Where Your Cat Lives, and you can keep hitting the "Random Cat" button to find more real cats all over the world. 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