Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mapping the Interactome

04.12.2014

Proteomics reveals the E-cadherin interaction network

Researchers at the Mechanobiology Institute at the National University of Singapore have comprehensively described the network of proteins involved in cell-cell adhesions, or the cadherin interactome. This work was published in Science Signaling (Guo et al. E-cadherin interactome complexity and robustness resolved by quantitative proteomics, Science Signaling, 02 Dec 2014, Vol 7, Issue 354).


Mechanobiology Institute, National University of Singapore

Figure: Schematic representation of E-cadherin and interactome proteins at an adherens junction

Unlocking the complexity of cell adhesion

Many biological processes depend on the ability of cells to stick to one another. The formation of multicellular organisms and precise embryonic development rely on this property, as does the maintenance of healthy tissue. Defects in the ability of cells to adhere to one another have been found in many diseases, such as cancer, Alzheimer’s disease and cardiovascular disease. In the case of cancer, ineffective cell adhesion allows tumour cells to detach and invade other tissues, thereby spreading cancer throughout the body.

Cell-cell adhesion is made possible through various cellular structures that are collectively known as cell-cell adhesion complexes. The most prominent cell-cell adhesion complex is the Adherens Junction. Central to adherens junctions is a protein known as E-cadherin, or epithelial cadherin. E-cadherin spans the cell membrane, providing a link between the interior, and exterior of the cell.

Outside the cell, E-cadherin binds to other E-cadherins from neighbouring cells in a mechanism that can be described as a ‘cellular handshake’. On the inside of the cell, E-cadherin binds to linker proteins known as catenins, which attach to a structural scaffold that lies adjacent to the adhesion site, the actin cytoskeleton. This physical link between the cytoskeletons of neighboring cells allows for the generation and transduction of mechanical signals.

Despite their importance in cell-cell adhesion, scientists have yet to fully understand how the cadherin-catenin-actin complex forms and is regulated. To extend the idea of cell adhesion being like a ‘cellular handshake’, imagine walking along a crowded street while holding hands with a partner. Moving together with the flow of people, navigating obstacles, adjusting your speed and responding to changes in conditions must all be considered if you are to reach your destination without letting go.

Similarly, cells must maintain their adhesion while facing varying stresses and biochemical conditions. Hence, the adhesive structures are regulated and adjusted, via a complex network of structural and regulatory proteins. Where defective adhesion has led to a certain disease it is essential to understand where the problem lies and this requires stepping back and looking at the whole picture.

To better identify the components of this wider network in maintaining and regulating adhesion, researchers at the Mechanobiology Institute, National University of Singapore, applied a combination of experimental and computational techniques to reveal and dissect the complex network of proteins that interact with E-cadherin. To achieve this, E-cadherin was labelled with an enzyme that, when activated, releases a small cloud of a tagging molecule to flag all other proteins in the immediate vicinity. When coupled with quantitative proteomics, this provides a list of proteins interacting with E-cadherin, thus capturing many of the proteins that influence the adhesive properties of the cell.

Overall 561 proteins were found to be associated with E-cadherin, and remarkably 419 of these interactions were completely novel. Using a protein interaction database, the researchers created a map of the E-cadherin interactome that contains information on the function of each protein and its interactions with other proteins within the network. The majority of proteins found were identified as adaptor proteins, which serve as scaffolds within the Adherens Junction. Other proteins involved in cellular transport and protein synthesis were also identified. Interestingly, the researchers found that most of the proteins that associated with E-cadherin did so independently of cell-cell adhesion.

This study highlights that cell adhesion results not only from the formation of a cadherin-catenin-actin complex, but from the activity of more than 500 interacting proteins. Successful cell adhesion requires a cascade of events involving these proteins and any breakdown in this cascade could lead to impaired cell adhesion, and disease. With the E-cadherin interactome now described in detail, researchers can finally step back and view the complex picture that is cell-cell adhesion. This will allow disease related defects to be identified, and new targets researched to understand this vital biological process.

Contact Information
Amal Naquiah
amal@nus.edu.sg
Phone: +65 6516 5125

Amal Naquiah | newswise
Further information:
http://www.nus.edu.sg

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>