Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell Death: How a Protein Drives Immune Cells to Suicide

15.07.2016

For some pathogens, attack is the best form of defense – they enter immune cells of the human body. However, if they are detected in their hidden niche, the infected cell kills itself to re-expose the pathogens. In the “EMBO Journal” a research group at the University of Basel’s Biozentrum has reported that a protein called gasdermin forms permeable pores in the cell membrane and thus triggers the suicide of the immune cell.

The best hiding place often lies behind enemy lines, as many bacteria such as the pathogens responsible for tuberculosis or typhoid have realized. They invade immune cells and can survive there, well hidden, for some time. To eliminate such invaders, the host macrophages can initiate a suicide program.


Mechanism of pore formation by the protein gasdermin D, resulting in cell death.

University of Basel, Biozentrum


Atomic force microscopy image of the pore.

University of Basel, Biozentrum

Together with researchers at the Novartis Institute for Biomedical Research and ETH Zurich, the team led by Prof. Sebastian Hiller from the Biozentrum at the University of Basel has shown for the first time that a “death protein” perforates the cell membrane, resulting in macrophage bursting open. The re-exposed pathogens can then again be fought by the immune system.

Gasdermin D: Executioner in the cell

Tiny cell components of invading pathogens are recognized by receptors inside macrophages. These, in turn, activate a signaling cascade, which triggers an inflammatory response and initiates pyroptosis – a specific form of programmed cell death.

“Some studies have already demonstrated that the protein gasdermin D plays a central role in pyroptosis,” explains Prof. Petr Broz, one of the main authors of the study. “We have now discovered how gasdermin drives immune cells to suicide and using cryo-electron and atomic force microscopy we could visualize the pores in the cell membrane.”

The protein gasdermin D is at the end of a long signaling pathway. Intracellular receptors recognizing foreign bacterial components induce the assembly of the inflammasome. This protein complex, in turn, activates enzymes that generate active gasdermin fragments by proteolytic cleavage.

“In the macrophages, gasdermin D is the executioner, which carries out the death sentence,” says Hiller, clarifying the role of the protein. “The cleaved gasdermin D fragments rapidly target the cell membrane of macrophages and permeabilize it by forming a pore. The porous membrane leads to cell swelling and bursting.”

Gasdermins cooperate in cell suicide

With gasdermin D, the researchers have not only identified the protein that deals a deathblow to immune cells, but they could also visualize pore formation using high-resolution microscopy techniques. As it turns out, following the cleavage of gasdermin D only one of the two fragments is required for the seamless integration into the cell membrane.

So far, only little is known about the gasdermin family of proteins, which along with gasdermin D includes five other members. In the future, Hiller’s team aims to investigate the structure and function of several gasdermins to determine whether and how they cooperate in pore formation and to identify the physiological context in which these proteins induce pyroptotic cell death.

Original source

Lorenzo Sborgi, Sebastian Rühl, Estefania Mulvihill, Joka Pipercevic, Rosalie Heilig, Henning Stahlberg, Christopher J. Farady, Daniel J. Müller, Petr Broz and Sebastian Hiller
GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death
EMBO Journal; published online 14 July 2016, doi: 10.15252/embj.201694696

Further information

Prof. Sebastian Hiller, University of Basel, Biozentrum, tel. +41 61 267 20 82, email: sebastian.hiller@unibas.ch

Dr. Katrin Bühler, University of Basel, Communications Biozentrum, Tel. +41 61 267 09 74, email: katrin.buehler@unibas.ch

Heike Sacher | Universität Basel
Further information:
http://www.unibas.ch

Further reports about: Cell cell death cell membrane immune cells macrophages pathogens proteins

More articles from Life Sciences:

nachricht Fish recognize their prey by electric colors
13.11.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection
13.11.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

The dawn of a new era for genebanks - molecular characterisation of an entire genebank collection

13.11.2018 | Life Sciences

Fish recognize their prey by electric colors

13.11.2018 | Life Sciences

Ultrasound Connects

13.11.2018 | Awards Funding

VideoLinks
Science & Research
Overview of more VideoLinks >>>