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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>