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 New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>