Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Clues point to cause of a rare fat-distribution disease

21.03.2013
Novel modification of structural protein implicated

Studying a protein that gives structure to the nucleus of cells, Johns Hopkins researchers stumbled upon mutations associated with familial partial lipodystrophy (FPLD), a rare disease that disrupts normal patterns of fat distribution throughout the body.

"Our findings open new paths for learning how and why fat cells are disproportionately affected by mutations in the protein lamin A, which is found in the nucleus of most cells of the body," says Katherine Wilson, Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine.

According to the researchers, this is the first report that another protein, SUMO1, can attach to lamin A. Importantly, they found that FPLD-causing mutations in lamin A prevent this attachment. Details of the study were published in the Feb. 1 issue of the journal Molecular Biology of the Cell.

Wilson says lamin A is primarily known for giving shape to the nucleus. "It forms networks of strong 'cables' at the nuclear membrane and works with other proteins to create and maintain the three-dimensional environment in which chromosomes are properly organized, protected and expressed," she says.

When the Wilson group made their discovery, they were studying lamin A binding to another protein, actin. Actin can sometimes form a complex with certain SUMO proteins, small proteins often attached to other proteins to alter their functions, their locations and their interactions with additional proteins.

"Sometimes you go into an experiment looking for one thing but you find another," says Wilson. "We wanted to know if lamin A could bind to actin-SUMO1 complexes. Instead, we found that SUMO1 itself attaches to lamin A."

SUMO1 is usually attached to proteins at sites with certain properties; these sites can be predicted by the surrounding amino acids, the basic building blocks of proteins whose blueprints are found in genes. So the researchers searched lamin A's amino acid sequence for predicted binding sites and found five. Using targeted genetic techniques, they created lamin A variants, each with a mutation at a different predicted SUMO1 attachment site. They then added SUMO1 to the mutants and tested whether it could attach to them or not.

Two mutations significantly decreased SUMO1 attachment. One was at a predicted site; the other was unexpectedly in their comparison "control" variant. "Since the mutation site in our control variant was not a predicted SUMO1 attachment site, we were curious about it," explains Wilson. "Mutations in lamin A cause more than 15 different diseases, so we checked the genetic database to see if any diseases were associated with mutations near the SUMO1 attachment site, and FPLD leapt out like a neon sign."

FPLD is a very rare condition that starts around puberty. Fat on the legs of patients is reduced while it accumulates at other locations, including the neck and face. Patients can also become diabetic.

Twenty-four different mutations in lamin A can cause FPLD. To see if two other FPLD-causing mutations near the SUMO1 attachment site affected SUMO1 attachment, the team created these variants and tested them as before. One of the new variants did show decreased SUMO1 attachment. Based on the location of that mutation and one of the other SUMO1-disrupting mutations, the researchers were able to identify a "patch" on the surface of the lamin A protein that is important for SUMO1 attachment.

Exactly how lamin A and SUMO1 connect to FPLD is still a mystery. "We can only speculate on how lamin A and SUMO1 work together to regulate fat cells," says Wilson. "But these results raise new research questions that will hopefully move FPLD studies forward."

Other authors of the report include Dan Simon of the Johns Hopkins University School of Medicine and Tera Domaradzki and Wilma Hofmann of the University at Buffalo, The State University of New York.

This work was supported by grants from the National Institute of General Medical Sciences (RO1 GM048646) and the Department of Defense CDMRP (PC111523).

On the Web:

Link to article: http://dx.doi.org/10.1091/mbc.E12-07-0527

Wilson Lab: http://www.hopkinsmedicine.org/cellbio/dept/WilsonProfile.html

Related stories:

Promising Pursuits: Name That Field (the final story of the article) http://www.hopkinsmedicine.org/news/publications/johns_hopkins_health/spring_2011/promising_pursuits

Media Relations and Public Affairs
Media Contacts: Catherine Kolf; 443-287-2251; ckolf@jhmi.edu
Vanessa McMains; 410-502-9410; vmcmain1@jhmi.edu
Shawna Williams; 410-955-8236; shawna@jhmi.edu

Catherine Kolf | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht New technique unveils 'matrix' inside tissues and tumors
29.06.2017 | University of Copenhagen The Faculty of Health and Medical Sciences

nachricht Designed proteins to treat muscular dystrophy
29.06.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making Waves

Computer scientists use wave packet theory to develop realistic, detailed water wave simulations in real time. Their results will be presented at this year’s SIGGRAPH conference.

Think about the last time you were at a lake, river, or the ocean. Remember the ripples of the water, the waves crashing against the rocks, the wake following...

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Nanostructures taste the rainbow

29.06.2017 | Physics and Astronomy

New technique unveils 'matrix' inside tissues and tumors

29.06.2017 | Life Sciences

Cystic fibrosis alters the structure of mucus in airways

29.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>