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 Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>