Featured Research

from universities, journals, and other organizations

'Garbage disposal' role of VCP and implications for degenerative disease

Date:
December 27, 2009
Source:
Rockefeller University Press
Summary:
New research reveals how a mutant ATPase blocks autophagy partway through to cause a multi-tissue degenerative disease.

It's important to finish what you start, say Jeong-Sun Ju and researchers from Washington University School of Medicine, St. Louis. In the December 14, 2009 issue of the Journal of Cell Biology, Ju et al. reveal how a mutant ATPase blocks autophagy partway through to cause a multi-tissue degenerative disease.

Mutations in VCP, a member of the AAA ATPase family, cause inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD), a rare disorder that mainly affects skeletal muscle, brain, and bone. Patient muscle contains aggregates of membrane and proteins called rimmed vacuoles, which accumulate and disrupt cellular architecture. This pileup of membranous trash is inconsistent with VCP's known involvement in proteasome-mediated protein degradation. Ju et al. thus wondered whether the ATPase might also be involved in garbage disposal via the autophagy pathway.

Knocking down or expressing mutated VCP in cells increased levels of the autophagy markers p62 and LC3. Microscopy revealed that although autophagosomes containing these two proteins formed, they failed to mature into autolysosomes capable of degradation. VCP mutant mice and IBMPFD patients also accumulated p62 and LC3 in their muscle, and the two proteins localized to rimmed vacuoles, suggesting that the membrane-protein aggregates arise from frustrated autophagosomes. Indeed, injecting wild-type mice with a drug that blocks autophagosome maturation also produced rimmed vacuoles, as well as inducing other markers of IBMPFD myopathy.

The researchers now want to determine the mechanism by which VCP promotes the final stages of autophagy and how this is perturbed in IBMPFD patients. However, senior author Chris Weihl points out that many therapies being developed to treat degenerative diseases attempt to rescue cells by stimulating autophagy. In the case of IBMPFD, this could make matters worse, as autophagy has no problem initiating -- it's the failure to finish that causes the problem.


Story Source:

The above story is based on materials provided by Rockefeller University Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jeong-Sun Ju, Rodrigo A. Fuentealba, Sara E. Miller, Erin Jackson, David Piwnica-Worms, Robert H. Baloh, and Conrad C. Weihl. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. The Journal of Cell Biology, 2009; 187 (6): 875 DOI: 10.1083/jcb.200908115

Cite This Page:

Rockefeller University Press. "'Garbage disposal' role of VCP and implications for degenerative disease." ScienceDaily. ScienceDaily, 27 December 2009. <www.sciencedaily.com/releases/2009/12/091214101353.htm>.
Rockefeller University Press. (2009, December 27). 'Garbage disposal' role of VCP and implications for degenerative disease. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2009/12/091214101353.htm
Rockefeller University Press. "'Garbage disposal' role of VCP and implications for degenerative disease." ScienceDaily. www.sciencedaily.com/releases/2009/12/091214101353.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
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