Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cellular cleansing: ARF6, a protein indispensable for the elimination of waste and pathogens

25.06.2003


Like all living organisms, cells ingest foreign bodies, but not always as nutrients. Ingestion is also used to eliminate pathogens such as bacteria or harmful cellular waste. This cell function, known as phagocytosis, is vital, notably to the immune and inflammatory response.


Target enveloping :Once cellular waste are recognized and anchored on membrane;; the assembly of actin filaments starts. The membrane progressively engulfs the waste; what needs a supply of membranes from various internal cellular compartments.When the membrane folds fuse;; the waste is completely ingested by the cell and rendered harmless


Target cells ingested by white blood cells : On picture A;; the white blood cell (big cell) recognised some target cells (little white spheres) to eliminate and anchored them on its membrane. 50 minutes later (picture B);; target cells have been ingested. On pictures C;;D;; and E the white blood cell expresses a mutant type of ARF6 blocked in inactive position. On picture C;; the white blood cell recognised other white blood cells to eliminate and anchored them on its membrane. On picture D;; taken 50 minutes later;; target cells are still anchored on the white blood cell’s membrane and haven’t been ingested. On picture E;; the extension of the membrane starts but stops soon. Absorption doesn’t occur.



CNRS research scientists at the Institut Curie have recently clarified the function of the protein ARF6 in phagocytosis, a mechanism which is still poorly understood. When ARF6 is lacking, the cells can eliminate neither waste nor pathogenic microorganisms. This breakdown in the "cell cleaning" system may then result in major dysfunction (infection, inflammation) or even compromise the organism’’s integrity (risk of tumor).

These results are presented in the 23 June 2003 issue of Journal of Cell Biology.


Cells sometimes employ surprising means to eliminate particulates that threaten the body’’s equilibrium: they ingest and then digest them. This is achieved by phagocytosis when the particles exceed 250 nm in size. These may be cell debris, aging or damaged cells, or bacteria. In mammals, this "cellular cleansing" is done by certain categories of immune cells: macrophages, neutrophils and dendritic cells. Macrophages, for example, ingest more than 100 billion senescent red blood cells every day.

Phagocytosis is a cell function essential to the immune and inflammatory response:
  • it avoids inflammatory reactions by removing cell debris generated by apoptosis or necrosis;
  • it affords protection against infections by capturing and destroying bacteria.

In the case of chronic infection or inflammation, the body’s equilibrium is compromised and there is even the risk of the development of tumors. In particular, a link has been established between Helicobacter pylori infection and the development of gastric cancer, but the mechanisms brought into play in this model of oncogenesis remain poorly understood.

A very recent American publication has provided a clue to the putative link between chronic inflammation and the appearance of cancer: in mice whose phagocytic and immune functions are deficient, chronic infections lead to the growth of spontaneous tumors when the animals are not treated with antibiotics. This is new proof of the importance of phagocytosis, for good functioning of the body.

Envelop then degrade

When "cleaning cells" recognize a target to be eliminated, using their membrane receptors, they anchor it to the membrane. Phagocytosis then starts with the formation of membrane folds, a sort of envelope which progressively engulfs the target until it is internalized within the cell.

The gradual formation of a membrane requires reorganization of actin filaments, the "muscles" of the cell, and remodeling of the membrane. The assembly (polymerization) of actin filaments "pushes" the membrane around the cellular waste by a process analogous to that seen in cell motility (see "Further information on").

To enlarge the surface area of the membrane so as to allow enfolding of cellular waste, a supply of membranes from various internal cellular compartments is indispensable. When the waste is fully enveloped, the membrane folds fuse thereby completely ingesting the waste and rendering it harmless. The waste is then conveyed to vesicles where it is degraded. At this stage antigens are processed and once transported to the surface of cells, will trigger the immune response (acquired immunity).

At the Institut Curie, Philippe Chavrier’’s "Membrane and cytoskeleton dynamics" team is studying the reorganization of the membrane and of the cytoskeleton during phagocytosis. It is focusing in particular on the protein ARF6, which is thought to play a part in phagocytosis and in cell motility, and whose precise function remains to be elucidated.

ARF6 "delivers" membranes

Like many proteins, ARF6 works as a "biological switch" flicking successively between the inactive and active states, during which it fulfils its functions. In this new work, Florence Niedergang of Philippe Chavrier’’s team has demonstrated for the first time that ARF6 is activated during phagocytosis, at the start of the process, suggesting that it plays a part in the early stages of the engulfing of waste.

To study this hypothesis further, researchers at the Institut Curie studied phagocytosis by scanning electron microscopy in cells where ARF6 is blocked in the inactive position. They found that the extension of the membrane around the waste is soon stopped. Furthermore, they noted that the interruption was not due to blockade of actin polymerization but to defective delivery of membranes from the intracellular compartments.
ARF6 therefore plays a crucial role in the delivery of membranes during phagocytosis.

As phagocytosis and cell motility share several features (see below), ARF6 could also be indispensable to cell motility and may be involved in the formation of metastases. The presence of metastases renders cancer treatment more problematical, and so it is important to identify the proteins that participate in this process and which could in time serve as targets for new therapies.

The work of Philippe Chavrier and his team at the Institut Curie therefore provides fundamental information on the mechanisms of phagocytosis, while providing a glimpse of new leads in the understanding of cancerous processes.

Catherine Goupillon | Institut Curie
Further information:
http://www.jcb.org

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>