Selective Motor Proteins Drive Macromolecular Transport in Mature Epithelial Cells

Cell biologists have found that transport of cell membrane proteins from their point of manufacture inside the cell to their correct location on the cell surface depends on the selective action of specific "motor proteins.” Drugs causing inhibition of specific motor proteins could provide more effective, targeted therapies with fewer side effects in diseases such as cancer and cystic fibrosis.

Cell surface markers are among the various macromolecules, cellular organelles, and vesicles that are transported by kinesins. Kinesins are a group of related motor proteins that use a microtubule track along which to "walk.” They are vital to movement of chromosomes during mitosis and are also responsible for shuttling macromolecules, mitochondria, Golgi bodies, and vesicles within eukaryotic cells. Kinesins typically contain two heavy chains with motor heads that move along microtubules via a pseudo-processive asymmetric walking motion that can be towards the plus-end or the minus-end, depending on the type of kinesin. Fourteen distinct kinesin families are known, with some additional kinesin-like proteins that cannot be classified into these families.

Investigators at Weill Cornell Medical College (New York City, NY, USA) used advanced time-lapse microscopy to study the transport of membrane proteins in immature and mature epithelial cells. They reported in the October 9, 2007, issue of the journal Developmental Cell that the process differed between the immature and mature cells. In the mature cells, where polarity had been established, apical protein transport depended on selective microtubule motors. However, the kinesins involved were different than those that had transported the same protein in the immature cells.

"Not only are many more kinesins present in cells than previously thought, but their selectivity helps direct which packages of surface proteins are transported, as well as their ultimate destinations,” explained senior author Dr. Geri Kreitzer, assistant professor of cell and developmental biology at Weill Cornell Medical College. "Breakdown in these types of intracellular trafficking pathways is a serious contributing factor to many diseases ranging from cystic fibrosis to cancer. So, a better understanding of processes directed by the specific kinesin family members marks a big step forward in developing therapeutics that might someday treat or cure these illnesses. By targeting the individual motors rather than the tracks along which they all move [a current approach used to treat some types of cancer], we could bypass some of the effects on global cellular function that affect patients adversely.”


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