Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

912 Chapter 16: The Cytoskeleton
actin filaments and
fimbrin
actin filaments and
α-actinin
50 nm
(A)
parallel bundle
tight packing prevents myosin II
from entering bundle
contractile bundle
loose packing allows myosin II
to enter bundle
(B)
100 nm
polarized actin filaments into loose bundles, allowing the binding of myosin and
formation of contractile actin bundles (Figure 16–23). Because of the very different
spacing and orientation of the actin filaments, bundling by fimbrin automatically
discourages bundling by α-actinin, and vice versa, so that the two types of
bundling protein are mutually exclusive.
The bundling proteins that we have discussed so far have straight, stiff connections
between their two actin-filament-binding domains. Other actin cross-linking
proteins have either a flexible or a stiff, bent connection MBoC6 m16.49/16.23
between their two
binding domains, allowing them to form actin filament webs or gels, rather than
actin bundles. Filamin (see Figure 16–22) promotes the formation of a loose
and highly viscous gel by clamping together two actin filaments roughly at right
angles (Figure 16–24A). Cells require the actin gels formed by filamin to extend
the thin, sheetlike membrane projections called lamellipodia that help them to
crawl across solid surfaces. In humans, mutations in the filamin A gene cause
defects in nerve-cell migration during early embryonic development. Cells in the
periventricular region of the brain fail to migrate to the cortex and instead form
nodules, causing a syndrome called periventricular heterotopia (Figure 16–24B).
Interestingly, in addition to binding actin, filamins have been reported to interact
with a large number of cellular proteins of great functional diversity, including
membrane receptors for signaling molecules, and filamin mutations can also lead
to defects in development of bone, the cardiovascular system, and other organs.
Thus, filamins may also function as signaling scaffolds by connecting and coordinating
a wide variety of cellular processes with the actin cytoskeleton.
A very different, well-studied web-forming protein is spectrin, which was first
identified in red blood cells. Spectrin is a long, flexible protein made out of four
elongated polypeptide chains (two α subunits and two β subunits), arranged so
that the two actin-filament-binding sites are about 200 nm apart (compared with
14 nm for fimbrin and about 30 nm for α-actinin; see Figure 16–23). In the red
blood cell, spectrin is concentrated just beneath the plasma membrane, where it
forms a two-dimensional weblike network held together by short actin filaments
whose precise lengths are tightly regulated by capping proteins at each end; spectrin
links this web to the plasma membrane because it has separate binding sites
for peripheral membrane proteins, which are themselves positioned near the lipid
bilayer by integral membrane proteins (see Figure 10–38). The resulting network
creates a strong, yet flexible cell cortex that provides mechanical support for the
overlying plasma membrane, allowing the red blood cell to spring back to its original
shape after squeezing through a capillary. Close relatives of spectrin are found
in the cortex of most other vertebrate cell types, where they also help to shape and
stiffen the surface membrane. A particularly striking example of spectrin’s role
Figure 16–23 The formation of two
types of actin filament bundles.
(A) Fimbrin cross-links actin filaments into
tight bundles, which exclude the motor
protein myosin II from participating in the
assembly. In contrast, α-actinin, which is
a homodimer, cross-links actin filaments
into loose bundles, which allow myosin
(not shown) to incorporate into the bundle.
Fimbrin and α-actinin tend to exclude
one another because of the very different
spacing of the actin filament bundles that
they form. (B) Electron micrograph of
purified α-actinin molecules. (B, courtesy
of John Heuser.)