Policing proteins around the cells

Studying the 'motor cops' that carry nutrients and proteins into and out of the body's cells helps us understand how several …

Studying the 'motor cops' that carry nutrients and proteins into and out of the body's cells helps us understand how several diseases are caused, writes Dick Ahlstrom

Getting biochemical traffic into and out of cells is a complex business that is fundamental to health. When things go wrong with the mechanisms used to transport materials across the cell wall, diseases as varied as diabetes, BSE and cancer can be the result.

University College Cork cell biologist Dr Mary McCaffrey studies the "motor cops" that regulate this essential traffic. She is a senior lecturer in the biochemistry department of UCC's Biosciences Institute and also a Science Foundation Ireland investigator with a budget of more than €1 million to conduct research into this area.

It is all about "how materials get through a cell membrane", Dr McCaffrey explains. Nutrients, iron, growth factors and signalling proteins move into and out of cells all the time in a tightly regulated system called endocytosis.

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"There is a very sophisticated system in place in order to move materials into cells. We work on the proteins that control the movement of these materials and also how they recycle," she says.

"Recycling is a very specific term in cell transport. A protein moves from the cell surface into the cell where a decision is made whether to degrade the protein or recycle it back to the surface."

She likens each cell to an individual country with border police guarding the frontiers. Specialised transporter proteins sit ready to grab hold of materials and then guide them across the cell membrane and into the cell. Once they have the intended effect they are either recycled back outside the cell for reuse or broken down and discarded.

Dr McCaffrey's lab is involved in the search for the transporter proteins and any other proteins that respond to them. She has discovered families of proteins known to oversee the process including some of the group known as Rab proteins.

Among others she has studied Rab4, Rab25 and Rab11, with the latter two being particularly important given their linkages to cancers.

Rab is known to be upregulated in many cancers and also affects the aggressiveness of the disease in the breast and ovaries, McCaffrey says.

"The Rab protein dictates the aggressiveness of cancers," she adds. "The functional role of Rab11 isoforms in cancer is an area we are well placed to investigate with the extensive panel of reagents that we have developed over the years."

Rab is important in other diseases as well, she says. "Many diseases come about through a malfunction of membrane trafficking." She cites diabetes as one example, because Rab11 mediates the take-up of sugars into the cells.

BSE is another, given one theory yet to be proven that the normal prion is converted into the abnormal, BSE causing form after transport across the cell membrane.

She is currently seeking additional funding for the purchase of specialised equipment that will aid in her search for more Rab family members and the proteins they affect. One device is a form of "molecular microscope" that will allow the team to monitor individual protein behaviour.

"The more you understand the movement of materials within the cells the more chance you can control that movement," she says.