Cystic fibrosis (CF) is most commonly caused by deletion of a single amino acid (ΔF508) in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This mutation causes protein misfolding and disrupts many cellular functions. Many models of CFTRΔF508 misfolding exist, but none are amenable to rapid genetic dissection of the pathways that are disrupted by the mutation. He et al. now report a fluorescence-based C. elegans model that will enable such studies. They show that expressing the ΔF508 mutation in P-glycoprotein-3 (PGP-3), which is similar to mammalian CFTR, disrupts protein folding and prevents CFTR trafficking to the apical membrane of epithelial cells; this resembles the effects of the CFTRΔF508 mutation, and is rescued by the same treatments as in mammalian cells. This model will enable unbiased genetic screens for modulators of CFTR misfolding and hopefully uncover new therapeutic targets. Page 930
- Written by editorial staff. © 2012. Published by The Company of Biologists Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
DMM and COVID-19
We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.
Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.
The twin pillars of Disease Models & Mechanisms
In her first Editorial as Editor-in-Chief, Liz Patton sets out her vision and priorities for DMM focusing on four thematic challenges: mechanisms of disease, innovative technologies, disease progression through time and therapy.
Extended deadline - The RAS Pathway: Diseases, Therapeutics and Beyond
Our upcoming special issue is welcoming submissions until 3 May 2021. Guest-edited by Donita Brady (Perelman School of Medicine at the University of Pennsylvania, USA) and Arvin Dar (Icahn School of Medicine at Mount Sinai, USA), the issue will focus on the targeting the RAS pathway.
Find out more about the issue and how to submit your manuscript.
Perspective - Modelling the developmental origins of paediatric cancer to improve patient outcomes
James Amatruda authors our first Perspective, discussing some of the key challenges in paediatric cancer from his perspective as a physician-scientist.
A muscle growth-promoting treatment based on the attenuation of activin/myostatin signalling results in long-term testicular abnormalities
In this issue’s Editor’s choice, Ketan Patel and colleagues describe how even brief exposure to muscle-growth-promoting treatments exerts a long-term detrimental effect on the testes, and test promising therapeutics to mitigate this side-effect.