Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salk scientists uncover how a cell's 'fuel gauge' promotes healthy development

26.04.2016

Salk scientists have revealed how a cellular "fuel gauge" responsible for monitoring and managing cells' energy processes also has an unexpected role in development. This critical link could help researchers better understand cancer and diabetes pathways.

This cellular fuel gauge is a protein complex called AMPK that oversees energy input and output to keep the cell running smoothly. If AMPK were a car sensor, for instance, it would be able to instruct the vehicle when to get gas or lower the air conditioning to save energy.


Salk scientists reveal a close association between lysosomes, the recycling centers of the cell, and the development of the endodermal germ layer. This image shows a well-differentiated structure derived from normal embryonic stem cells, with all nuclei stained blue. Only endoderm cells (green) contain high levels of lysosomes (red).

Credit: Anwesh Kamireddy/Salk Institute

Similarly, if the cell's fuel supply--nutrients--is scarce, AMPK slows down cell growth and changes its metabolism. Previously, Salk Professor Reuben Shaw discovered that AMPK could halt tumors' revved-up metabolism, as well as restore normal function to the liver and other tissues in diabetics.

"Even though there's great interest in AMPK related to diabetes and cancer, frankly nothing was known about how this fuel gauge process changes in different cell populations during development," says Shaw, senior author of the work and holder of the William R. Brody Chair. Aside from giving new insight into stem cell therapies, the work, published in March 2016 in Genes & Development, could also help refine cancer treatments.

"To begin, we used CRISPR technology to edit out two important components of the AMPK pathway in embryonic stem cells," says Nathan Young, Salk research associate and first author of the paper. "At first we didn't see any difference, but things became interesting when we prompted the cells to differentiate."

Normally, embryonic stem cells have the capacity to generate more specialized cells that belong to one of three broad groups termed germ layers--the endoderm, ectoderm and mesoderm--that can ultimately develop into all of the diverse cell types in an organism. However, the cells without a functioning AMPK pathway failed to efficiently make endoderm (the innermost layer in an organism) and instead made too much ectoderm (the layer that would turn into skin).

"These cells couldn't make the right choice," says Shaw. "This was the first inclination that this metabolic pathway is telling cells what kind of specialized tissues to become."

What was remarkable, according to the researchers, is when they looked closer at the gene expression patterns of the AMPK-deficient cells. They found that a large number of down-regulated genes related to one specific cellular structure: the lysosome. This critical self-contained organelle contains corrosive enzymes that degrade cellular material to reuse components--the garbage disposal and recycling center of the cell.

This loss of lysosomes, the researchers discovered, was due to the loss of a transcription factor called Tfeb, which turns on the expression of lysosomal genes in times of starvation. By simply reintroducing Tfeb into the dysfunctional cells, the team was able to restore normal development and differentiation.

"It was thought that lysosomes and AMPK were connected somehow, but no one had dreamed that you'd get no lysosomes if you don't have this fuel gauge," says Shaw. "Connecting the AMPK pathway to lysosomes begs the question of whether this pathway is part of anti-cancer pathways as well."

Currently, lysosome inhibitors are in dozens of clinical trials for breast, lung, pancreatic and brain cancers, even though the exact link between lysosomes and tumors are not understood. "We are decoding some of these underlying connections that might indicate when and how a cancer drugs might be useful," says Shaw. "This work may also help up make better, more specific ways of targeting lysosomes in cancer."

###

Other authors were Anwesh Kamireddy, Jeanine Van Nostrand, Lillian Eichner, Maxim Nikolaievich Shokhirev and Yelena Dayn, all of the Salk Institute. The work was supported by the National Institutes of Health and the Leona M. and Harry B. Helmsley Charitable Trust.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin.

Media Contact

Salk Communications
press@salk.edu
858-453-4100

 @salkinstitute

http://www.salk.edu 

Salk Communications | EurekAlert!

Further reports about: embryonic stem embryonic stem cells genes lysosome lysosomes stem cells tumors

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 >>>