Biology Reference
In-Depth Information
Proteins that promote disassembly of actin filaments or cap filament barbed
ends play roles in actin dynamics and cell motility. Actin assembly can be
initiated by: (1) de novo nucleation (or stabilization of nuclei) with the
involvement of the Arp2/3 complex and (2) by Rac and phosphoinositide-
regulated release of capping and/or severing proteins of the gelsolin/villin
family (CapG, gelsolin, villin and adseverin), and the CapZ family of capping
proteins, from the barbed ends of actin filaments. Actin filament severing by
gelsolin family or ADF/cofilin family proteins could also in itself be a
mechanism for generating more free barbed ends from existing filaments.
How can villin enhance actin dynamics during cell motility?
There are a number of different types of actin-based motility. Different cells
seem to move using different strategies. However, there are some general
properties of cell movement. In general, the leading edge of a moving cell is
the main site of actin assembly and crosslinking (or gelation, a type of
'solidification' of the cytoplasm). The leading edge of an animal cell can
display a variety of types of protrusion: lamellipodia, filopodia (also known as
microspikes) and pseudopodia. In general, behind the protrusive structure,
there is a region of active actin disassembly, where filaments are shortened and
crosslinks disrupted. Actin monomers resulting from this disassembly appear
to then flow forward, where they can be added to the barbed ends of
polymerizing filaments at the leading edge. Treadmilling allows continuous
polymerization at barbed (plus) ends while disassembling continuously at
pointed (minus) ends, without net increase in polymer mass. This type of
polymerization can exert force and push out the plasma membrane during
protrusion or power the movement of intracellular bacteria (e.g. Listeria,
S. flexneri ).
ADF/cofilin proteins appear weakly to sever filaments without capping and
could perhaps generate new free barbed ends to support polymerization.
These proteins are most active not directly adjacent to the leading edge of
motile cells but somewhat behind it, and these ends would be rapidly capped
since there are high concentrations of capping proteins in the typical cell. The
ends would have to be uncapped or prevented from being capped in the first
place (by phosphoinositides) to support further elongation, which again
would make uncapping a major control point for generation of free barbed
ends from existing filaments. Certainly for villin that severs filaments, capping
is indeed an essential activity which also means that subsequent uncapping is
necessary for existing filaments to elongate. Actin disassembly generally
occurs behind the leading edge and can be mediated by proteins of both the
calcium-activated gelsolin family and the calcium-independent ADF/cofilin
family (also known as actophorin, destrin or depactin). The mechanism of
