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 Biophysicists reveal how optogenetic tool works
29.05.2020 | Moscow Institute of Physics and Technology

nachricht Mapping immune cells in brain tumors
29.05.2020 | University of Zurich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>