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 23, 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 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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


Health & Medicine

Mind & Brain

Living & Well

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