Researchers at the University of Illinois at Chicago show how a newly discovered molecular motor helps a cell determine which way is up.
The study was published in the July 31 issue of the Journal of Cell Biology.
The sense of top and bottom is often lost in cells that become cancerous and may be an important factor in metastasis.
Cells depend on the location of a number of proteins and lipids to recognize and maintain their polarity. Moving these lipids and proteins from where they are produced to where they are needed is a dynamic process.
Dr. Athar Chishti, professor of pharmacology at the UIC College of Medicine and principal investigator of the study, said researchers knew that a lipid called PIP3 is very important in signalling polarity. But the process everyone wanted to understand, he said, "was the trafficking and disposition of this lipid to where it was needed at the growing tips of the cells."
Chishti's research team, including Kaori Horiguchi and Dr. Toshihiko Hanada, determined that one domain of a molecular motor protein called a kinesin that they had discovered interacted with PIP3 binding protein. They showed that the kinesin and this binding protein motored the PIP3 along microtubules -- the tracks upon which the kinesins move their cargoes.
They also showed that the kinesin-binding adaptor and PIP3 were found together at the tips of the nerve cells and that in one of these cell types these molecules were most abundant in the longest extension, called the axon.
"We found the motor, the binding domains and an adaptor," said Chishti. "When the adaptor binds PIP3, it is delivered to the membrane where it is needed, and if you block this process, polarity is lost."
In some cells, like neurons, there are dramatic differences in the structure and function of the different ends of a cell. But even in cells where the difference between the ends is not as obvious, the delivery process is essential. Loss of cell polarity is often the first step in converting a normal cell to a cancer cell, Chishti said.
The discovery illuminates a key step in the trafficking and disposition
of polarity determinants. Science magazine highlighted the Chishti
paper as an Editor's Choice in the August 18th issue and in this week's Signal Transduction Segment online at
"Now we know the cargo, and we know the motor," said Chishti. "The next step will be to find out what turns the motor on and tells it to start down the track to deliver the cargo.
"In the kinesin field, there are two fundamental questions: what are the cargoes, and what turns the motors on and off that carry them."
Yasuhisa Fukui, of the University of Tokyo, also contributed to the study, which was funded by grants from the National Institutes of Health, Bethesda, Md. Hanada was the recipient of a Campus Research Board Award from UIC.
UIC ranks among the nation's top 50 universities in federal research funding and is Chicago's largest university with 25,000 students, 12,000 faculty and staff, 15 colleges and the state's major public medical center. A hallmark of the campus is the Great Cities Commitment, through which UIC faculty, students and staff engage with community, corporate, foundation and government partners in hundreds of programs to improve the quality of life in metropolitan areas around the world.
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