entirely as F-actin. In muscle this is in fact the case,
but in non-muscle cells the actin filaments are constantly turned over and are in dynamic equilibrium
with the free G-actin monomers. The regulation of
this equilibrium as well as the functional organization
of the actin filaments and their reorganization during
normal cell function is apparently the task of a complex group of proteins found particularly in nonmuscle cells in association with actin monomers and
filaments. The structural and functional properties of
the actin-binding proteins have by no means been
determined in detail. More than 60 such proteins
from various tissues have been described and more
are being added to this list. Many of the known actinbinding proteins are probably ubiquitous but comparative biochemical data are not yet available. As there
are as yet very few sequence data, nothing can be
said at present about the evolution of these proteins,
and the number of protein super-families involved
cannot be estimated. It can be assumed, however,
that every cell contains representatives of different
families of actin-binding proteins [224, 265].
According to the types of interaction with
actins, the actin-binding proteins can be ordered
into function classes with some overlap. Many of
these proteins bind actin monomers and thus inhibit polymerization. The "capping" proteins
deposit themselves on only one end of the filament, usually the B end. Finally, there are proteins which bind along the length of the actin filaments and these are also of different sorts: one
binds like tropomyosin to only one filament,
whilst others are divalent and form filament networks or bundles [224]. In the especially wellinvestigated cells of Acanthamoeba, one or more
representatives of all classes have been found [46].
The best-known monomer-binding proteins are
the pro .... lins, which have been detected in several
isoforms in various mammalian cells (spleen cells,
macrophages, brain cells), sea urchin eggs, sperm
of the holothurian Thyone, as well as in Tetrahymena, Acanthamoeba and the slime mould Physarum. Profilins bind only to actin monomers, and
not to dimers or higher polymers, and have a
greater affinity for ATP-actin than ADP-actin.
Their inhibitory effect on polymerization cannot
involve reduction of the monomer concentration
alone; the dissociation constant of the actinprofilin complex is so high that even in the presence of profilin the monomer concentration
exceeds the critical concentration. Sequence data
are available for human profilin, for a basic profilin from calf spleen (142 amino acids), and for
two acidic and one basic isoform from Acanthamoeba (all with 125 amino acids). The profilins
10.5 Actin-Binding Proteins
343
contain trimethyllysine but have no other similarities to actin [4, 64, 152, 224, 276]. Further
monomer-binding proteins have been isolated
from the amoeba: these include the homodimer
actobindin (two units of 13 kDa), which in contrast to the Acanthamoeba profilin also reacts
with rabbit actin, and the monomeric actophorin
(15 kDa), which is not related to profilin and
unlike the latter protein can also bind F-actin
[46, 156]. Cofilin (166 amino acids), from various
mammalian and chicken tissues, and the homologous destrin also bind F-actins in addition to
actin monomers [2, 194].
Most capping proteins bind to the B end of the
filament, but the exact mechanism of their effect
is not clear. These proteins may inhibit association or accelerate dissociation at the occupied
end. In particular, they may bring about the de
novo synthesis of shorter filaments with occupied
(capped) ends; several of them have a filamentsevering effect. The biological significance of
these actin-binding proteins may lie in the stabilization of a certain filament length, preventing the
otherwise constant process of addition to the B
end and reduction of the P end (the "actin treadmill"). The intracellular concentration of the capping proteins is sufficient to occupy all the available actin filaments [224]. There are apparently
three proteins families in this functional class:
1. The capping proteins in the narrowest sense;
these are heterodimers with subunits of
30-35 kDa, known not only from Acanthamoeba, slime moulds and vertebrate nonmuscle cells but also from vertebrate skeletal
muscle [29, 224].
2. The fragminlseverin family (monomers of
45 kDa) is found in slime moulds, thyroid cells
and sea urchin eggs.
3. The gelsolinlvillin family (monomers of
90-95 kDa) is as yet known only in the vertebrates.
Proteins from the latter two families are regulated
by calcium and also have filament-cleaving properties. Brevin from the blood plasma is encoded
by the same gene as that which encodes the intracellular gelsolin, but it has N-terminal extensions
of 9 amino acids in the pig and 25 amino acids in
man [151,301]. The proteins binding to the Pend
of actin filaments are not so well known. They
include, for example, acumentin from macrophages (63.5 kDa), ~ actinin from mammalian
skeletal muscle (35-37 kDa), and also cytoskeleton proteins such as spectrin and the band-4.1
protein (p. 360). Smaller filament-cleaving proteins
but in non-muscle cells the actin filaments are constantly turned over and are in dynamic equilibrium
with the free G-actin monomers. The regulation of
this equilibrium as well as the functional organization
of the actin filaments and their reorganization during
normal cell function is apparently the task of a complex group of proteins found particularly in nonmuscle cells in association with actin monomers and
filaments. The structural and functional properties of
the actin-binding proteins have by no means been
determined in detail. More than 60 such proteins
from various tissues have been described and more
are being added to this list. Many of the known actinbinding proteins are probably ubiquitous but comparative biochemical data are not yet available. As there
are as yet very few sequence data, nothing can be
said at present about the evolution of these proteins,
and the number of protein super-families involved
cannot be estimated. It can be assumed, however,
that every cell contains representatives of different
families of actin-binding proteins [224, 265].
According to the types of interaction with
actins, the actin-binding proteins can be ordered
into function classes with some overlap. Many of
these proteins bind actin monomers and thus inhibit polymerization. The "capping" proteins
deposit themselves on only one end of the filament, usually the B end. Finally, there are proteins which bind along the length of the actin filaments and these are also of different sorts: one
binds like tropomyosin to only one filament,
whilst others are divalent and form filament networks or bundles [224]. In the especially wellinvestigated cells of Acanthamoeba, one or more
representatives of all classes have been found [46].
The best-known monomer-binding proteins are
the pro .... lins, which have been detected in several
isoforms in various mammalian cells (spleen cells,
macrophages, brain cells), sea urchin eggs, sperm
of the holothurian Thyone, as well as in Tetrahymena, Acanthamoeba and the slime mould Physarum. Profilins bind only to actin monomers, and
not to dimers or higher polymers, and have a
greater affinity for ATP-actin than ADP-actin.
Their inhibitory effect on polymerization cannot
involve reduction of the monomer concentration
alone; the dissociation constant of the actinprofilin complex is so high that even in the presence of profilin the monomer concentration
exceeds the critical concentration. Sequence data
are available for human profilin, for a basic profilin from calf spleen (142 amino acids), and for
two acidic and one basic isoform from Acanthamoeba (all with 125 amino acids). The profilins
10.5 Actin-Binding Proteins
343
contain trimethyllysine but have no other similarities to actin [4, 64, 152, 224, 276]. Further
monomer-binding proteins have been isolated
from the amoeba: these include the homodimer
actobindin (two units of 13 kDa), which in contrast to the Acanthamoeba profilin also reacts
with rabbit actin, and the monomeric actophorin
(15 kDa), which is not related to profilin and
unlike the latter protein can also bind F-actin
[46, 156]. Cofilin (166 amino acids), from various
mammalian and chicken tissues, and the homologous destrin also bind F-actins in addition to
actin monomers [2, 194].
Most capping proteins bind to the B end of the
filament, but the exact mechanism of their effect
is not clear. These proteins may inhibit association or accelerate dissociation at the occupied
end. In particular, they may bring about the de
novo synthesis of shorter filaments with occupied
(capped) ends; several of them have a filamentsevering effect. The biological significance of
these actin-binding proteins may lie in the stabilization of a certain filament length, preventing the
otherwise constant process of addition to the B
end and reduction of the P end (the "actin treadmill"). The intracellular concentration of the capping proteins is sufficient to occupy all the available actin filaments [224]. There are apparently
three proteins families in this functional class:
1. The capping proteins in the narrowest sense;
these are heterodimers with subunits of
30-35 kDa, known not only from Acanthamoeba, slime moulds and vertebrate nonmuscle cells but also from vertebrate skeletal
muscle [29, 224].
2. The fragminlseverin family (monomers of
45 kDa) is found in slime moulds, thyroid cells
and sea urchin eggs.
3. The gelsolinlvillin family (monomers of
90-95 kDa) is as yet known only in the vertebrates.
Proteins from the latter two families are regulated
by calcium and also have filament-cleaving properties. Brevin from the blood plasma is encoded
by the same gene as that which encodes the intracellular gelsolin, but it has N-terminal extensions
of 9 amino acids in the pig and 25 amino acids in
man [151,301]. The proteins binding to the Pend
of actin filaments are not so well known. They
include, for example, acumentin from macrophages (63.5 kDa), ~ actinin from mammalian
skeletal muscle (35-37 kDa), and also cytoskeleton proteins such as spectrin and the band-4.1
protein (p. 360). Smaller filament-cleaving proteins