molecules of more than 250 kDa. These include
MAP1 with 330-350 kDa and MAP2 with
280-300 kDa; MAP1 is bound to three light
chains of 34, 31 and 18 kDa in the bovine brain.
The second group of MAPs are the tau factors,
which are tissue- and stage-specific proteins of
55-62 kDa that include in their sequence of
341-383 amino acids three or four typical, Cterminal 31-residue repeats [85, 150, 160,244,
305]. In the parasitic flagellate Giardia, the protofilaments formed from microtubules bear bandlike protein structures. The predominant protein
of the bands, ~ giardin, consists of 259 amino acids
whose sequence includes 35 seven-residue repeats
(heptads) and forms an a-helical coiled-coil [110].
10.10 Proteins of Intermediary Filaments
In addition to actin microfilaments and tubulin,
the cytoskeleton of almost all eukaryotic cells
contains a third type of filament which, with diameters of 8-12 nm, are larger than microfilaments (5-6 nm) but smaller than microtubules
(23-25 nm), and are therefore known as intermediary filaments (IF). In contrast to the actin
filaments and microtubules, these are stable
structures which are not subject to constant
switching between elongation and shortening. On
the basis of their occurrence in cells of different
types and of the properties of their protein components, six classes ofIFproteins are recognized:
1. About 30 different cytokeratins of 40-70 kDa
in epithelial cells and their derivatives, and
also in liver cells.
2. Desmins (52 kDa) in different muscle types.
3. Vimentins (53 kDa) in cells of mesenchymal
origin.
4. Glia fibril acidic proteins (GFAPs) of
45-55 kDa in glial cells (astrocytes).
5. The triplet of the neurofilament (NF) proteins: NF-L (68 kDa) , NF-M (150 kDa) and NFH (200 kDa).
6. Lamins (60-80 kDa) from the lamina of the
nucleus.
A special feature of the vimentins is that they
occur in embryonic or tissue-culture cells together with, or instead of, the cell-specific IF proteins. Thus, vimentin is found with desmin in
embryonic myotubules, and together with cytokeratins in cultures of epithelial cells. The cells of
the mammalian germline are amongst the few cell
types without IFs; in contrast, the oocytes of
10.10 Proteins of Intermediary Filaments
355
amphibians contain both vimentins and cytokeratins [87, 212,244].
Despite their many differences, the IF proteins
have some common characteristics; in particular,
they are all weakly soluble under normal physiological conditions, and both in vivo and in vitro
they form morphologically similar filaments.
Copolymeric filaments of desmin and vimentin
not only arise in vitro but are also found naturally
in the wall cells of blood vessels and in the myoblasts of chicken embryos. The basic structural
unit of the IF is apparently a complex of four
chains which, in pairs, form two coiled-coil structures. All IF proteins have in their centre a conservative a-helical rod domain of about 310
amino acids, flanked by variable, non-helical
domains. The central domains are made up of
four segments of uniform size (lA, 1B, 2A and
2B), which consist of seven-amino acid repeats
(heptads) of similar sequences and which produce
the coiled-coil structure of the dimers, and three
linkers of varying lengths (Ll, L12 and L2), which
have no tendency to form coiled coils (Fig. 10.8).
In order for two a-helical peptide chains to
form a coiled-coil, they must be built repetitively
of heptads with non-polar amino acids in the first
and fourth positions. IF proteins can be categorized into four types according to their heptad
sequences and the structure of their terminal
domains. The cytokeratins can be divided into
acidic (type I) and basic (type II); vimentin, desmin and GFAP make up type III and the NF proteins type IV [74,244, 261]. The amino acid
sequences of type-I cytokeratins have less in common with type II (26-28 %) than with vimentin
and GFAP (36-37 %); in contrast, desmin,
vimentin and GFAP agree in 60-70 % of positions [9, 136]. It was only recently discovered that
the lamins A and C from the lamina of the cell
nucleus also belong to the super-family of the IF
proteins. They also form dimers with a coiled-coil
structure; however, these do not associate into
long filaments. Because of differences in the
structure of the rod domains, lamins A and C do
not fit into any of the classes I-IV, and they are
designated type V [180, 214].
All the known IF genes occur as only one copy
in the genoJIle. However, several mRNAs arise
from the chicken vimentin gene by use of at least
three poly(A)-regions, which all code for the
same protein [261, 320]. The genes for cytokeratins, desmin, vimentin and GFAP have similar
structures with eight or nine (cytokeratin I)
exons; the genes for NF-L with four exons and
NF-M with three exons have a very different
MAP1 with 330-350 kDa and MAP2 with
280-300 kDa; MAP1 is bound to three light
chains of 34, 31 and 18 kDa in the bovine brain.
The second group of MAPs are the tau factors,
which are tissue- and stage-specific proteins of
55-62 kDa that include in their sequence of
341-383 amino acids three or four typical, Cterminal 31-residue repeats [85, 150, 160,244,
305]. In the parasitic flagellate Giardia, the protofilaments formed from microtubules bear bandlike protein structures. The predominant protein
of the bands, ~ giardin, consists of 259 amino acids
whose sequence includes 35 seven-residue repeats
(heptads) and forms an a-helical coiled-coil [110].
10.10 Proteins of Intermediary Filaments
In addition to actin microfilaments and tubulin,
the cytoskeleton of almost all eukaryotic cells
contains a third type of filament which, with diameters of 8-12 nm, are larger than microfilaments (5-6 nm) but smaller than microtubules
(23-25 nm), and are therefore known as intermediary filaments (IF). In contrast to the actin
filaments and microtubules, these are stable
structures which are not subject to constant
switching between elongation and shortening. On
the basis of their occurrence in cells of different
types and of the properties of their protein components, six classes ofIFproteins are recognized:
1. About 30 different cytokeratins of 40-70 kDa
in epithelial cells and their derivatives, and
also in liver cells.
2. Desmins (52 kDa) in different muscle types.
3. Vimentins (53 kDa) in cells of mesenchymal
origin.
4. Glia fibril acidic proteins (GFAPs) of
45-55 kDa in glial cells (astrocytes).
5. The triplet of the neurofilament (NF) proteins: NF-L (68 kDa) , NF-M (150 kDa) and NFH (200 kDa).
6. Lamins (60-80 kDa) from the lamina of the
nucleus.
A special feature of the vimentins is that they
occur in embryonic or tissue-culture cells together with, or instead of, the cell-specific IF proteins. Thus, vimentin is found with desmin in
embryonic myotubules, and together with cytokeratins in cultures of epithelial cells. The cells of
the mammalian germline are amongst the few cell
types without IFs; in contrast, the oocytes of
10.10 Proteins of Intermediary Filaments
355
amphibians contain both vimentins and cytokeratins [87, 212,244].
Despite their many differences, the IF proteins
have some common characteristics; in particular,
they are all weakly soluble under normal physiological conditions, and both in vivo and in vitro
they form morphologically similar filaments.
Copolymeric filaments of desmin and vimentin
not only arise in vitro but are also found naturally
in the wall cells of blood vessels and in the myoblasts of chicken embryos. The basic structural
unit of the IF is apparently a complex of four
chains which, in pairs, form two coiled-coil structures. All IF proteins have in their centre a conservative a-helical rod domain of about 310
amino acids, flanked by variable, non-helical
domains. The central domains are made up of
four segments of uniform size (lA, 1B, 2A and
2B), which consist of seven-amino acid repeats
(heptads) of similar sequences and which produce
the coiled-coil structure of the dimers, and three
linkers of varying lengths (Ll, L12 and L2), which
have no tendency to form coiled coils (Fig. 10.8).
In order for two a-helical peptide chains to
form a coiled-coil, they must be built repetitively
of heptads with non-polar amino acids in the first
and fourth positions. IF proteins can be categorized into four types according to their heptad
sequences and the structure of their terminal
domains. The cytokeratins can be divided into
acidic (type I) and basic (type II); vimentin, desmin and GFAP make up type III and the NF proteins type IV [74,244, 261]. The amino acid
sequences of type-I cytokeratins have less in common with type II (26-28 %) than with vimentin
and GFAP (36-37 %); in contrast, desmin,
vimentin and GFAP agree in 60-70 % of positions [9, 136]. It was only recently discovered that
the lamins A and C from the lamina of the cell
nucleus also belong to the super-family of the IF
proteins. They also form dimers with a coiled-coil
structure; however, these do not associate into
long filaments. Because of differences in the
structure of the rod domains, lamins A and C do
not fit into any of the classes I-IV, and they are
designated type V [180, 214].
All the known IF genes occur as only one copy
in the genoJIle. However, several mRNAs arise
from the chicken vimentin gene by use of at least
three poly(A)-regions, which all code for the
same protein [261, 320]. The genes for cytokeratins, desmin, vimentin and GFAP have similar
structures with eight or nine (cytokeratin I)
exons; the genes for NF-L with four exons and
NF-M with three exons have a very different