Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein complex found to regulate first step in human blood clotting

03.06.2002


Brown scientists have described a previously unknown but critical blood-clotting role for Arp2/3, a complex of seven proteins found in animal and plant cells.



Reporting in the June 15 issue of Blood, the scientists show that Arp2/3 complex is a cellular machine that drives a human blood platelet to change shape into a larger, more flattened form and begin the process of clotting. The link between what happens at the surface of a platelet and the mechanism of shape change within it has mystified scientists for decades. Arp2/3 has been found in yeast and a soil amoeba, as well as platelets.

“A major question for scientists has been how to control platelet shape change,” said the project’s senior researcher, Elaine Bearer, M.D., associate professor of pathology and laboratory medicine. “Understanding these molecular events could lead to better treatments for abnormal clotting.” Roughly 80 percent of strokes are caused by atypical clots that block blood flow.


Bearer and colleagues found that Arp2/3 complex is required for platelets to form the shape-changing filaments that begin the blood clotting process. The process of filament formation is called actin polymerization.

Actin filaments are fine threads composed of multiple subunits – polymers that line up like a sting of pop beads – which give structure to the cell, as well as drive shape changes, cell movements and other cellular processes. These filaments also participate in muscle contractions. The formation of filaments inside dividing cells also separates cytoplasm into the two daughter cells, so that each inherits the right amount of maternal material.

Since the first cell was observed under a microscope more than 200 years ago, scientists have sought to explain cellular shape change. Cell shape is used today for the pathologic diagnosis of tumors such as breast cancer. For 50 years, scientists have known that actin was required for shape change. Until now, they were unable to explain what drove actin to polymerize and form filaments.

Polymerization of actin is an important first step in the process of platelet clot formation. Platelets use these filaments to reach out and grab fibrin, the major matrix material of clots, and other platelets, to form the clots.

When a blood vessel is torn, molecules are released that bind to platelet surface receptors. This creates a cascade of events inside the first platelets that arrive at the wound, which change shape, sending out sticky arms into the blood flow to recruit other platelets that attach in an organized matrix to stop the bleeding and maintain the vessel.

Stroke, which results from abnormal clotting, is treated with blood thinning compounds to block platelets from forming clots. “A problem with this therapy is that it may completely stop platelet activity and a person may bleed to death,” Bearer said. “We would like to find a gentler way to block polymerization without this dangerous side effect.”

Cell biologists guessed that Arp2/3 complex played a role in nucleating new actin filaments because it did so in a test tube. Although many proteins play a similar role in test tubes, none has been found to be required in cells. Bearer and colleagues are the first to demonstrate that Arp2/3 complex plays a central role in nucleating actin filaments inside a cell.

“We think there are about 10 biochemical events between the cell and the polymerization process,” she said. “Each step triggers the next event in a pathway that culminates in polymerization. We’d like to learn how to control this process.”

Actin polymerization occurs in cells across the class of creatures called eukaryota. These include all animals, plants, fungi, algae and protozoa. Eukaryota share fundamental characteristics of cellular organization, biochemistry and molecular biology.

“Showing that the Arp2/3 complex is a major regulator in platelet actin dynamics leads us to believe that it plays this role in all cells, because all cells have shape-changing abilities that are required for many vital cell processes,” Bearer said. “Beyond representing a significant advance in the understanding of molecular events leading to platelet shape change, this work is likely to provide fundamental information about the principles and paradigms governing actin dynamics inside all cells.”

The Brown scientists developed new molecular-insertion technology – a model for testing the internal mechanisms of cells – to help them describe both the role of Arp2/3 as well as where it is located and activated during the stages of filament formation. The technology allowed researchers to “reach inside and tickle” the tiny platelets, without destroying them.

“It made it possible to manipulate the molecular composition of the platelet cytoplasm,” Bearer said. “This allowed us to investigate biochemical relationships between signaling pathways and the shape changes that occur in platelets but are common to all cells. The method provides a new model to test the effect of small molecules on signal pathways and shape changes in other human cells and other cell types.”

Besides Bearer, the research team included Zhi Li, lead author and doctoral student, and undergraduate Eric Kim. Both Li and Kim graduated in May 2002. Funding from the National Institutes of General Medical Sciences of the National Institutes of Health, a Salomon Research Award and the Brown University Undergraduate Teaching and Research Assistantships Program supported the work.

Scott Turner | EurekAlert

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 >>>