Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A switch that makes a blood clot sticky found within the platelet membrane

02.05.2003


One key to platelet integrin receptor found in transmembrane region



Integrin receptors allow cells to attach to other cells and to connective tissue which is necessary to form tissues, organs, or even people, for that matter. Researchers at the University of Pennsylvania School of Medicine have demonstrated that a key to activating αIIbβ3, the integrin that allows platelets to form blood clots, can be found in the part of the molecule embedded within a platelet’s outer membrane.

The αIIbβ3 integrin, also known as the platelet fibrinogen receptor or GP IIb-IIIa, has been the focus of an entire class of blood-thinning drugs, called GPIIb-IIIa agonists. The Penn researchers findings, published in this week’s issue of Science, have implications for drugs created to thin the blood and, perhaps more broadly, offer an intriguing hint as to how integrins on cells throughout the body may function.


"The part of the GPIIb-IIIa molecule that is embedded in the fatty layers that constitute the platelet’s outer membrane can determine whether or not the integrin is activated, thereby making the platelet ’sticky,’" said Joel S. Bennett, MD, Professor in Penn’s Division of Hematology/Oncology within the Department of Medicine. "The transmembrane region, which was generally assumed to be just an anchor for keeping the integrin receptor in place, can be an activating switch for the entire molecule."

Once activated, the two subunits of GPIIb-IIIa that extend outside the cell can clasp the walls of a damaged blood vessel or a passing fibrinogen molecule ¡V much like a bobby pin can close around strands of hair ¡V thereby forming a normal blood clot or a pathologic thrombus. GPIIb-IIIa agonist drugs, such as ReoPro®, Integrilin®, and Aggrastat®, work by preventing activated GPIIb-IIIa from binding to other objects in the bloodstream.

Since it is a protein, GPIIb-IIIa is made up of amino acids, strung along in a specific sequence to give the protein its shape. Bennett and his colleagues were able to determine which amino acids are responsible for activating GPIIb-IIIa by substituting a ’wrong’ amino acid at spaces along the  protein chain and expressing the mutant protein in cells growing in culture. They found that the transmembrane portion of one of the GPIIb-IIIa subunits is responsible for responding to activation signals and, in return, causing groups of the activated integrin to cluster.

"Remarkably, these regions are evolutionarily conserved ¡V meaning the transmembrane region in GPIIb-IIIa is the same in apes or rabbits or mice as they are in humans," said Bennett. "That tells us that the sequences of the transmembrane region of integrins are important factors in how these proteins function."

Moreover, nearly every integrin has a different transmembrane region made up of a unique amino acid sequence. If the transmembrane regions of all integrins work on a similar scheme, it would provide a new paradigm for the function of integrins and other cell membrane proteins.

"Integrin receptors are more than just a cellular form of Velcro ¡V as integrins bind, they can also generate signals that command a cell to act, such as whether to divide or differentiate or to produce an important protein such as a gene transcription factor," said Bennett. "It will be interesting, and even medically important, to determine how these signals can be modulated."

Other scientists involved in the research paper described here include Renhao Li, Neal Mitra, Holly Gratkowski, Gaston Vilaire, Reustem Litvinov, Chandrasekaran Nagasami, John Weisel, James D. Lear, and William F. DeGrado from Penn.

Greg Lester | EurekAlert!
Further information:
http://www.med.upenn.edu/

More articles from Life Sciences:

nachricht Historical rainfall levels are significant in carbon emissions from soil
30.05.2017 | University of Texas at Austin

nachricht 3D printer inks from the woods
30.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New Method of Characterizing Graphene

Scientists have developed a new method of characterizing graphene’s properties without applying disruptive electrical contacts, allowing them to investigate both the resistance and quantum capacitance of graphene and other two-dimensional materials. Researchers from the Swiss Nanoscience Institute and the University of Basel’s Department of Physics reported their findings in the journal Physical Review Applied.

Graphene consists of a single layer of carbon atoms. It is transparent, harder than diamond and stronger than steel, yet flexible, and a significantly better...

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

3D printer inks from the woods

30.05.2017 | Life Sciences

How circadian clocks communicate with each other

30.05.2017 | Life Sciences

Graphene and quantum dots put in motion a CMOS-integrated camera that can see the invisible

30.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>