Matthew Tyska, Ph.D., recalls being intrigued, from the first day of his postdoctoral fellowship in 1999, with a nearly 30-year-old photograph. It was an electron micrograph that showed the internal structures of an intestinal cell microvillus, a finger-like protrusion on the cell surface. Microvilli are common features on the epithelial cells that line the bodys cavities.

At the time, Tyska knew that the core bundle traveling up the center of the microvillus was an array of the structural protein actin, and that the ladder-like "rungs" connecting the actin bundle to the cell membrane were composed of the motor protein myosin-1a. This myosin, though related to the myosin involved in muscle cell contraction, was thought to serve a purely structural role. "The textbook thinking for decades was that microvilli serve as a passive scaffold, a way to amplify the membrane surface area," said Tyska, assistant professor of Cell and Developmental Biology at Vanderbilt University.

In the intestines, an expanded cell surface increases the space for nutrient-processing enzymes and transporters, offering greater capacity for nutrient handling. But it didn't make sense to Tyska that a motor protein a protein with the potential to generate force and move cargo around in cells would play a passive structural role. "When I looked at that image, the near crystalline arrangement reminded me of actin and myosin in a muscle fiber," Tyska said. "I kept returning to the same question: why would the microvillus have this beautiful structure packed with motor proteins. The concentration of myosin motors in a single microvillus is very high; theres serious force-generating potential there."

Tyska and Russell McConnell, a student in his laboratory, tested the idea that these motor proteins are more than molecular glue binding the cell membrane to the actin bundle" The investigators purified the intestinal brush border" the layer of densely packed microvilli from the
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Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
30-May-2007