Cell Nucleus Biogenesis, Structure and Function
395
are also found within the nuclear in-
terior.
In vivo
studies support the view
that these, like the peripheral proteins,
are assembled into structures that have
rather slow rates of exchange. However,
it is still unclear if this represents a
lamin Flament network that pervades the
nucleus or local aggregates of lamin pro-
teins that might serve a function that
does not demand a contiguous ‘‘nucleos-
keleton.’’
3.2.1
The Lamin Genes
The lamin proteins represent a small
protein
family
that
has
increased
in
complexity during metazoan evolution.
Simple eukaryotes, such as the yeast
S. cerevisiae
, do not have lamin proteins;
perhaps the lamina evolved during the
transition from a closed mitosis to open
mitosis. The simple multicellular organ-
ism
Caenorhabditis elegans
has a single
lamin gene, which is expressed in all so-
matic cells. Mammals have three lamin
genes (
LMNA, LMNB1
,and
LMNB2
)that
are processed to yield 7 isoforms. RNA
processing – alternative splicing – of the
LMNA
primary transcript generates four
A-type lamins – lamins A, A
±
10 (a splice
variant without exon 10), C, and C2. Three
B-type lamins, called
lamins B1–B3
,a
re
encoded by the
LMNB1/2
genes. All ver-
tebrate cells express at least one variant
o
ft
h
eB
-
t
y
p
el
am
i
np
r
o
t
e
i
n
s
.T
h
eA
-
type lamins, in contrast, are expressed
primarily in differentiated cells so that
p
a
t
t
e
rn
so
fl
am
in
sA
,A
±
10 and C ex-
pression are developmentally regulated.
Lamins C2 and B3 are found only in germ
cells.
3.2.2
The Lamin Proteins and Filament
Assembly
Like other members of the intermediate
Flament class of proteins, lamins have a
central rod domain that consists mainly
of heptad repeats. The coiled-coil struc-
ture that forms from these repeats drives
the interaction of two monomers to form
a coiled-coil dimer. This form is the ba-
sic building block for lamin Flaments.
Higher-order Flaments form as a conse-
quence of lateral interaction between the
rod domains of the dimers. The rod do-
mains are flanked by non-
α
-helical amino-
terminal and carboxy-terminal domains.
The latter contains a nuclear localization
signal. Lamin proteins are also subjected
to posttranslational modiFcations such as
phosphorylation and most importantly are
modiFed by isoprenylation, a modiFcation
that targets the lamin Flaments to the
nuclear envelope. This modiFcation takes
place on a special CaaX motif (not found in
lamin C). ±ollowing cleavage after the cys-
teine residue the new terminal amino acid
is modiFed by isoprenylation and methyl
esteriFcation.
3.2.3
Lamin Function
Various studies identify the structural fea-
tures as a major role for the lamin proteins.
It is notable, for example, that nuclei main-
tain their shape even after most of the
nuclear contents have been removed. This
and many other experiments suggest a role
for the lamins in maintaining the mechan-
ical stability of nuclei. The importance of
maintaining a particular nuclear shape is
not clear. Perhaps more important func-
tionally is the possibility that the nuclear
lamina can potentially deFne nuclear sites
that have particular functional roles. Many
proteins are known that act as adaptors
that link the lamina to the nuclear en-
velope and components within chromatin
to the lamina. Heterochromatin – which is
transcriptionally inert – is commonly asso-
ciated with the nuclear periphery and this
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