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

INTERMEDIATE FILAMENTS AND SEPTINS
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outer
nuclear
membrane
inner
nuclear
membrane
microtubule
nuclear
pore
chromosome
centrosome
motors
plectin
PERINUCLEAR
SPACE
nuclear lamina
actin
CYTOPLASM
KASH-domain
proteins
SUN-domain
proteins
NUCLEUS
Figure 16–72 SUN–KASH protein
complexes connect the nucleus
and cytoplasm through the nuclear
envelope. The cytoplasmic cytoskeleton
is linked across the nuclear envelope
to the nuclear lamina or chromosomes
through SUN and KASH proteins (orange
and purple, respectively). The SUN and
KASH domains of these proteins bind
within the lumen of the nuclear envelope.
From the inner nuclear envelope, SUN
proteins connect to the nuclear lamina
or chromosomes. KASH proteins in the
outer nuclear envelope connect to the
cytoplasmic cytoskeleton by binding
microtubule motor proteins, actin
filaments, or plectin.
of the inner nuclear membrane and KASH proteins (also called nesprins) of the
outer nuclear membrane (Figure 16–72). SUN and KASH proteins bind to each
other within the lumen of the nuclear envelope, forming a bridge that connects the
MBoC6 n16.404/16.74
nuclear and cytoplasmic cytoskeletons. Inside the nucleus, the SUN proteins bind
to the nuclear lamina or chromosomes, whereas in the cytoplasm, KASH proteins
can bind directly to actin filaments and indirectly to microtubules and intermediate
filaments through association with motor proteins and plakins, respectively.
This linkage serves to mechanically couple the nucleus to the cytoskeleton and is
involved in many cellular functions, including chromosome movements inside
the nucleus during meiosis, nuclear and centrosome positioning, nuclear migration,
and global cytoskeletal organization.
Mutations in the gene for plectin cause a devastating human disease that
combines epidermolysis bullosa (caused by disruption of skin keratin filaments),
muscular dystrophy (caused by disruption of desmin filaments), and neurodegeneration
(caused by disruption of neurofilaments). Mice lacking a functional
plectin gene die within a few days of birth, with blistered skin and abnormal skeletal
and heart muscles. Thus, although plectin may not be necessary for the initial
formation and assembly of intermediate filaments, its cross-linking action is
required to provide cells with the strength they need to withstand the mechanical
stresses inherent to vertebrate life.
Septins Form Filaments That Regulate Cell Polarity
GTP-binding proteins called septins serve as an additional filament system in all
eukaryotes except terrestrial plants. Septins assemble into nonpolar filaments
that form rings and cagelike structures, which act as scaffolds to compartmentalize
membranes into distinct domains, or recruit and organize the actin and
microtubule cytoskeletons. First identified in budding yeast, septin filaments
localize to the neck between a dividing yeast mother cell and its growing bud
(Figure 16–73A). At this location, septins block the movement of proteins from
one side of the bud neck to the other, thereby concentrating cell growth preferentially
within the bud. Septins also recruit the actin–myosin machinery that forms
the contractile ring required for cytokinesis. In animal cells, septins function in
cell division, migration, and vesicle trafficking. In primary cilia, for example, a
ring of septin filaments assembles at the base of the cilium and serves as a diffusion
barrier at the plasma membrane, restricting the movement of membrane
proteins and establishing a specific composition in the ciliary membrane (Figure
16–73B and C). Reduction of septin levels impairs primary cilium formation and
signaling.
There are 7 septin genes in yeast and 13 in human, and septin proteins fall
into four groups on the basis of sequence relationships. In a test tube, purified
septins assemble into symmetrical hetero-hexamers or hetero–octamers that