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 In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>