Dynamic Actin

By Jason Socrates Bardi


MIRANDA: O, wonder! How many goodly creatures are there here! How beauteous mankind is! O brave new world, That has such people in it!

———William Shakespeare, "The Tempest," 1611.


Some of the most exciting areas of research are those dynamic ones in which we are just embarking. Velia Fowler, who is a professor in the Department of Cell Biology, has spent several years studying how actin filaments work to stabilize the shape of a cell, and how actin filament organization is controlled by actin binding proteins.

"[I've been] interested in how the cell regulates actin polymerization and generates specific actin architectures in different cells," says Fowler.

Now Fowler will be pursuing a whole new direction in her research—investigating the dynamic properties of actin and how cells control the polymerization of actin to control cell motility, shape changing, crawling, and phagocytosis.

Muscles of Steel

Actin is a structural protein that forms filaments made up of monomers added one onto the other, and actin bundles or networks are groups of these fibers bound together with other proteins. Like the steel girders that stabilize a building beneath the glass and mortar, the different arrangements of actin filaments into bundles or networks are the supporting structures that give cells different morphologies, or shapes. These shapes go hand and hand with the functional properties of the cell, and an important part of development is the formation of the correct actin cytoskeleton.

"The form is designed for the function, and it's dependent on actin polymerization and the integration of actin filaments into higher-order structures," says Fowler.

Epithelial cells that line the intestines have long, finger-like projections into the intestine supported by bundles of actin filaments that increase the surface area of the intestinal lining. This improves the absorption of nutrients that are then transported through the blood stream.

Red blood cells, which are responsible for transporting oxygen through the bloodstream, have a two-dimensional network of short filaments of actin connected by linker proteins that give the cells their flattened, biconcave disc shape. This network is flexible and can be distorted so that a red blood cell can squeeze through capillaries one fourth their size.

Actin also plays a key role in the physiology of muscles. Heart and skeletal muscle cells have parallel bundles of actin filaments arranged end-to-end in long strings of regular repeating units called sarcomeres. In these sarcomeres, bipolar filaments of myosin, another protein fiber in muscles, pull on the opposing sets of actin filaments from each end to shorten the sarcomeres. This generates muscle contractions that powers the beating of the heart and movements of skeletal muscles. Remarkably, the lengths of the actin filaments in the muscle sarcomeres are held constant and do not vary over many cycles of contraction.

However, mechanical stress and other environmental cues influence this length.

For example, actin filament lengths in sarcomeres vary between fast and slow twitch skeletal muscles. Different muscle groups in the body have different combinations of fast and slow twitch muscles, and in athletes, the combination is largely determined by the type of training that they do. Long distance runners, for instance, have a different combination than sprinters. And if a runner were to switch from 100-yard dashes to marathons, his/her muscle groups would slowly adapt to the new demands.

"When you think of architecture, you think of something stable, fixed—a defined form," says Fowler. And even though cells have apparently stable actin filaments, they are not like steel girders—formed once and fixed in their shape. Instead, there are cycles of polymerization used by the cell to create structures and change their length as opposed to making completely new ones from scratch.

"Cells need to be plastic," she says. "They have to change in time and respond to physiological conditions."

This Candle Burns at Both Ends

Fowler is interested in what controls the length of an actin filament. She uses muscle cells to study the dynamics of actin filaments, since actin filaments in muscle are about one micron long, which can easily be viewed with a light microscope. "We can study the dynamics of actin in muscles—the engine that leads to the contraction—and we can study it as it happens," she says.

To do this, Fowler's research focuses on a protein that caps one end of the actin filaments and controls their length by controlling the subunit exchange of bound and free actin subunits.

Actin filaments are polarized, and the two ends are dissimilar both in terms of their appearance under a microscope and the types of other proteins that they bind to. The "barbed" end is where much of the subunit exchange takes place and where many different types of capping proteins, one of which was identified in the Fowler laboratory, exist to regulate this exchange. But the other, "pointed," end is what particularly holds Fowler's interest.


Next Page | Pointed End Capping

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Professor of Cell Biology Velia Fowler and 2000 TSRI graduate Ryan Littlefield using a falling ball viscometer to study actin polymerization. Photo by Michael Balderas.