Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Does a Heart Know When It’s Big Enough?

29.03.2010
A protein discovered in fruit fly eyes has brought a Johns Hopkins team closer to understanding how the human heart and other organs automatically “right size” themselves, a piece of information that may hold clues to controlling cancer.

The protein, named Kibra, is linked to a relay of chemical signals responsible for shaping and sizing tissue growth by coordinating control of cell proliferation and death, according to research published Feb. 16 in Developmental Cell by teams at Johns Hopkins and Florida State University.

In a series of experiments, the scientists manipulated Kibra’s role in a signaling network called the Hippo pathway, which consists of several proteins working together as a braking system. Counterparts of the components in the Hippo pathway in flies are found in most animals, suggesting that this pathway may act as a “global regulator” of organ size control, according to Duojia Pan, Ph.D., a professor of molecular biology and genetics at Johns Hopkins University School of Medicine and an investigator of the Howard Hughes Medical Institute.

“People have always been curious about what makes a hippopotamus grow so much bigger than a mouse,” says Pan, “as well as how our two hands, which develop independently, get to very similar sizes. Our studies show that Kibra regulates Hippo, which keeps organs characteristically sized, preventing my heart or your liver from becoming as hefty as those befitting a large African amphibious mammal,” he adds, referring to the signaling pathway’s name.

Pan's team identified the gene they named Hippo in 2003, showing that an abnormal copy of it led to an unusually large eye in a developing fruit fly. Two years later, the team established that Hippo lies in the middle of a signaling cascade: Its “stop growing” message is relayed along a molecular pathway of biochemically linked proteins, which limits the expression of genes that otherwise promote cell division and cell survival. In 2007, they showed that by manipulating the pathway in a mouse liver, the organ grew to five times its normal size and became cancerous.

The new experiments, Pan says, moved the investigation “slowly and methodically upstream” to find Hippo’s trigger, where, he believes, “the key to size-control lies.” The Hippo-Kibra link could be a key to understanding and treating cancer, Pan adds, because cancer is literally a disease of uncontrolled growth.

The Johns Hopkins and Florida State teams discovered Kibra by studying ovarian cells from adult flies and by using a gene-controlling technique called RNA interference (RNAi) to systematically turn off each of the approximately 14,000 genes in the fly genome, one at a time, in cultured fly cells. They then analyzed the function of Kibra in the developing fly larvae. Each of the specialized discs that develop into a fly’s eyes starts out with approximately 30 to 40 cells and then grows by about a thousand-fold in the larval stage before stopping, making larvae the ideal place to catch the right-sizing process in action, Pan says. These studies told them that the Hippo pathway was not active in the absence Kibra.

Further studies on human cells measured the activity of the Hippo pathway while manipulating human Kibra and showed that like its fruit fly counterpart, human Kibra acts as a tumor suppressor protein that regulates Hippo signaling.

“The discovery of Kibra moves us an important step closer to identifying the initial signal that triggers Hippo’s activation,” Pan says. “We’re making progress along the Hippo pathway, heading toward the cell surface, and believe we will find that elusive signal en route.”

The name Kibra, a shortened combination of the words kidney and brain, is based on earlier evidence that Kibra is prominently expressed in those two organs. Kibra’s role in memory performance in humans has already garnered interest.

Authors of the paper, in addition to Pan, are Jianzhong Yu, Stephen Klusza and Wu-Min Deng of Florida State University; and Yonggang Zheng and Jixin Dong of Johns Hopkins.

This research was supported by grants from the National Institutes of Health.

On the Web:
http://humangenetics.jhmi.edu/index.php/faculty/duojia-pan.html
http://www.cell.com/developmental-cell/

Maryalice Yakutchik | Newswise Science News
Further information:
http://www.cell.com/developmental-cell/
http://humangenetics.jhmi.edu/index.php/faculty/duojia-pan.html
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>