Biology Reference
In-Depth Information
Molecular Mechanisms
Regulating Actin Filament
Dynamics at the Leading Edge
of Motile Cells
Thomas D. Pollard
We have analysed the molecular basis of pseudopod extension using
biochemical and biophysical approaches. We and others have determined
the atomic structures of the key proteins including actin, profilin, Arp2/3
complex, capping protein and ADF/cofilin as well as the rate and equilibrium
constants for their interactions. Arp2/3 complex interacts with actin
monomers and filaments to generate new filament branches. A pool of actin
bound to profilin provides subunits to elongate the ends of the branches and
to push forward the plasma membrane. Capping protein terminates branch
elongation. ADF/cofilin and profilin promote the disassembly of older actin
filaments and the recycling of actin subunits to a pool ready for elongation of
new filaments.
Students of cellular motility, marvelled for years about how cells advance their
leading edges by spreading lamellae as they migrate over substrates and
through the extracellular matrix. After the discovery of actin in non-muscle
cells (Hatano and Oosawa, 1966), electron microscopy (Abercrombie et al.,
1971; Small et al., 1978; Svitkina et al., 1997) and later fluorescence
microscopy (Lazarides and Weber, 1974) revealed that actin filaments are
