Biology Reference
In-Depth Information
FIGURE 8.3 The geometry of actin's pressure on the plasma membrane.
The maximum practical length that a filament can protrude beyond its last anchor point is
about 150 nm, 1 and this means that new filaments must be produced constantly from the
actin network, and that the network itself must advance close behind the leading edge of
the cell.
New actin filaments are nucleated on the sides of existing actin filaments by the activity of
the Arp2/3 protein complex. 8 e 10 This complex caps the pointed end of new actin filaments
and allows their barbed ends to be free for new growth, and it directs the new filament at an
angle of 70 degrees to the axis of the mother filament. 11,12 Once nucleated, new filaments
grow by addition of actin to their barbed ends and continue to do so until their barbed
ends are capped by barbed end-capping proteins. The length of a new actin filament is there-
fore set by the relative probabilities of new monomer addition and barbed end capping. To
complicate matters, the rates of capping may not be spatially uniform since the activity of
barbed end-capping proteins is antagonized by phosphatidyl inositides such as PI-4-P and
PI-4,5-P 2 , which are located at the inner face of the plasma membrane (this will be discussed
further in Chapter 9). 13 Also, of course, barbed end capping of a filament directly abutting the
membrane can, like monomer addition, take place only when the filament is transitorily
sprung away from the membrane by the motion of the Brownian ratchet. This spatial modu-
lation of capping rates is useful because it allows filaments pushing usefully against the
membrane to be somewhat protected from capping while those that happen to be directed
uselessly away from the membrane are capped quickly and do not therefore grow and waste
reserves of actin ( Figure 8.4 ).
Arp2/3, which drives the production of new branches, is not constitutively active but
requires activation by other proteins such as WASP (Wiscott-Aldrich syndrome protein) 14
and SCAR. These proteins tend to be complexed to activating signal transduction molecules
at or very near the plasma membrane, and this means that Arp2/3 tends to be active only
near the plasma membrane so that new branches are only nucleated where they may be of
some use ( Figure 8.5 ). Together, these features of Arp2/3-driven actin branching produce
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