Focus
Spotlight
February 25, 2002
Cell Veil Lifted on Actin Activity
Speckle Method Reveals Individual Molecules in ActionAt various points in its life, a cell weaves one or more gauzy protrusions along its membrane. Unfurled in times of need--for example, when a neuron must make its way across the brain or when an immune cell has to chase down bacteria--these gossamer ruffles hold the secret to a central question in biology: how do cells move? Like many filmy structures, the lamellipodia hide more than they reveal.
Actin fibres, seen as fluorescent lines (top left and middle), were thought to grow only at the very edge of the lamellopodium. By tracking individual actin molecules (top right), Tim Mitichison and Naoki Watanabe (shown below) discovered actin polymerization throughout the lamellopodium. Curiously, newly formed actin filaments appear to move backward (videos top middle and right). "The cell tries to go forward, but the overall sense is a backward movment," said Mitchison. Rong Li believes that this apparent retrograde movement is due to the fact that the lamellopodia's leading edge is moving forward faster than the actin filaments, which are fixed to the substrate. The filaments look as though they are going backward, when in fact they are stationary. Images above courtesy of Naoki Watanabe. Photo below by Pam Murray.
For instance, it is known that lamellipodia are knit from filaments of the cell skeleton protein actin that essentially pull the cell along. But how do cells weave these sturdy diaphanous skirts? Do the actin fibers, which are spun together from single molecules, take shape at the hem or assemble throughout the length of the lamellipodia?
The popular scientific response has been that the actin molecules are joined together at the leading edge. In the Feb. 8 Science, HMS researchers Naoki Watanabe and Tim Mitchison offer a contradictory view. Using a method that allows them to trace individual fluorescing actin molecules, they have observed actin fibers forming throughout the lamellipodia.
It is an observation that does not quite make sense. Lamellipodia lie uniformly flat as they grow. Yet if new actin filaments are being produced throughout, the lamellipodia should become rounded in areas and bunch up. "I am puzzled--it's not the neat answer," said Mitchison, the Hasib Sabbagh professor of cell biology. "It says we don't understand the biochemistry as much as we might think. How does the lamellipodium maintain a constant thickness?"
What makes it even more puzzling is that earlier work by Mitchison and also by HMS colleagues Rong Li and Marc Kirschner has shown that key molecules needed to polymerize actin lie at the cell membrane. As is often the case, confusion is provoking new scenarios. "It's making people think and that is good," said Li, HMS associate professor of cell biology.
"There are always lots of stories about molecules and what they do, and Tim's is more a story about trying to understand how a whole ensemble of things functions," said Kirschner, the Carl W. Walter professor of cell biology.
--Misia Landau