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in maintaining cell shape. 10 The comparative simplicity of the mammalian erythrocyte allows
its shape to be modelled mathematically and the results of possible manipulations to be pre-
dicted. Other cells, however, have an elaborate cytoskeletal system internal to the cortex, in
addition to the cortical gel, and this plays a major role in morphogenesis. It is this internal
system that has attracted most attention in relation to the tensegrity model.
As described in Chapter 3, actin polymerizes spontaneously in vitro when it is sufficiently
concentrated, having to first form a dimer then a trimer. Formation of the trimer involves an
unfavourable reaction but, once the trimer is formed, polymerization is favourable. The two
ends of the filament elongate at different rates, the 'barbed' more rapidly than the 'pointed'
end (the terms 'barbed' and 'pointed' derive from the appearance of actin filaments deco-
rated with myosin). In conditions typical of a living cytoplasm, the rate of spontaneous
trimer formation is so low as to be insignificant and the nucleation of new filaments
depends on protein complexes that can stabilize or mimic trimers. These protein complexes
include Arp2/3 and proteins of the Formin family. Each type of complex is used to nucleate
specific types of microfilament and mutations cause loss of specific subsets. 11 e 13 Broadly,
Arp2/3 is used to nucleate branched networks of actin typical of the leading edges of motile
cells and of the cortical actin gel network, while Formins are used to nucleate straight
filaments. 14,15
The formation of cell-cell and cell-matrix junctions is intimately linked to the formation of
new microfilaments. As adherens junctions develop between epithelial cells, they recruit
a large number of proteins to the inside of the plasma membrane. These include Formin1,
which is linked to junctional cadherins via a -catenin. 16 Since Formin1 nucleates the formation
of unbranched actin filaments in vitro , 16 it seems likely that its localization in the inner face of
cell-cell junctions is important for ensuring that the pointed end of a microfilament is at the
junction. This idea is supported by the effects of transfecting cells with a chimaeric protein
that consists of the a -catenin-binding domain of Formin1 conjugated to green fluorescent
protein. This chimaera competes for a -catenin with Formin1 itself and displaces Formin1
from the junction ( Figure 5.5 ). Its presence destabilizes junctions and inhibits the formation
of actin cables.
Plasma membrane
Formins
E-cadherin
Actin
Actin
Growing filament
Vinculin
Catenins
E-cadherin
Catenins
CELL 1
CELL 2
CELL 1
CELL 2
FIGURE 5.5 Linkage between cadherins, catenins, Formins (left diagram), vinculin (right diagram) and
microfilaments at adherens junctions. The pointed/barbed polarity of actin is depicted by the chevrons in the actin
filament.
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