'Traffic' in our cells works both for and against us

May 1, 2013

A mechanism that permits essential substances to enter our cells while at the same time removing from them harmful components also has a "down side." This negative aspect prevents vital drugs, such as anti-cancer drugs, from achieving their designed functions, while also enabling bacterial cells to develop resistance to penetration of antibiotics.

A study aimed at a fuller understanding of how this selective mechanism works—with a view towards better controlling it through new drug designs—is the subject of an article by Hebrew University of Jerusalem and German researchers that. has been published in Proceedings of the National Academy of Sciences (PNAS).

The trafficking of materials in and out of cells is controlled by a variety of proteins found in the membrane surrounding living cells, called "transporters." It is these transporters that fulfill the important function of allowing entrance of vital compounds on the one hand and disposal of on the other hand.

While providing an essential survival strategy for the organism, the transporters that remove toxic compounds from the cell have been associated with the ability of the bacterial cell to develop resistance to antibiotics. In , transporters are responsible for some types of resistance of to antineoplastic drugs (drugs against abnormal/cancerous growths). Since this resistance poses serious problems in the treatment of cancers and infectious diseases, these proteins are an important target for drug design.

To progress in this pursuit, a more complete knowledge of the transporter mechanism is required, but despite many studies, this mechanism is not yet fully understood. It is, however, well established that an essential part of the mechanism stems from the ability of the transporter to change conformations. Thus, the binding site of a particular transporter is alternatively exposed either to the (interior) or to the outside environment, enabling the protein to bind its materials on one side of the cell and transport them to the other side.

The research conducted by the Hebrew University-German team focused at a model transporter expressed in the brain: VMAT (Vesicular MonoAmine Transporter). VMAT is known to transport a variety of neurotransmitters like adrenaline, dopamine and serotonin. In addition, it can also transport MPP, a neurotoxin involved in models of Parkinson's disease.

A functional and structural link between VMAT and bacterial transporters responsible for multidrug resistance may suggest a common origin for both types of proteins. A number of studies demonstrated the significance of VMAT as a target for drug therapy in a variety of pathologic states, such as high blood pressure, hyperkinetic movement disorders and Tourette syndrome.

Explore further: From shape-shifting to therapy

Related Stories

From shape-shifting to therapy

March 12, 2013
(Medical Xpress)—The latest research into the intricate processes that let substances into and out of cells will help to lay the foundations for the next generation of therapies for major diseases.

New research looks at novel ways to combat drug resistance

March 27, 2013
University of Southampton biological scientists are leading a major research project aimed at making drugs more effective.

Scientist discovers new target for cancer therapy

January 24, 2013
Tumour cells need far more nutrients than normal cells and these nutrients cannot get into the malignant cells without transporters.

Hot on the trail of metabolic diseases and resistance to antibiotics

March 28, 2012
Proteins belonging to the large and important family of ABC transporters have been associated with metabolic diseases and can cause resistance to antibiotics. Biochemists from the University of Zurich and the NCCR Structural ...

Mapping of cancer cell fuel pumps paves the way for new drugs

April 28, 2013
For the first time, researchers at Karolinska Institutet in Sweden have managed to obtain detailed images of the way in which the transport protein GLUT transports sugars into cells. Since tumours are highly dependent on ...

Discovery could reduce chemotherapy's side effects

March 11, 2012
A team of researchers at Duke University has determined the structure of a key molecule that can carry chemotherapy and anti-viral drugs into cells, which could help to create more effective drugs with fewer effects to healthy ...

Recommended for you

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.