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

998 Chapter 17: The Cell Cycle
Figure 17–43 The midbody. (A) A
scanning electron micrograph of a cultured
animal cell dividing; the midbody still joins
the two daughter cells. (B) A conventional
electron micrograph of the midbody of a
dividing animal cell. Cleavage is almost
complete, but the daughter cells remain
attached by this thin strand of cytoplasm
containing the remains of the central
spindle. (A, courtesy of Guenter Albrecht-
Buehler; B, courtesy of J.M. Mullins.)
(A)
10 µm
region of interdigitated interpolar microtubules
in midbody
cell A
cell B
inactive RhoA
GDP
RhoGAP
RhoGEF
GTP
active RhoA
(B)
remaining interpolar
microtubules from
central spindle
dense matrix material
plasma membrane
1 µm
formin
Rho-activated kinases
(including Rock)
be placed between the two sets of daughter chromosomes, thereby ensuring that
each daughter cell receives a complete set. The correct timing and positioning
of cytokinesis in animal cells are achieved by mechanisms that depend on the
mitotic spindle. During anaphase, the spindle generates signals that initiate furrow
formation at a position midway between the spindle poles, thereby ensuring
that division occurs between the two sets of separated chromosomes. Because
these signals originate in the anaphase spindle, this mechanism also contributes
to the correct timing of cytokinesis MBoC6 m17.51/17.43 in late mitosis. Cytokinesis also occurs
at the correct time because dephosphorylation of Cdk substrates, which depends
on cyclin destruction in metaphase and anaphase, initiates cytokinesis. We now
describe these regulatory mechanisms in more detail, with an emphasis on cytokinesis
in animal cells.
Studies of the fertilized eggs of marine invertebrates first revealed the importance
of spindle microtubules in determining the placement of the contractile
ring. After fertilization, these embryos cleave rapidly without intervening periods
of growth. In this way, the original egg is progressively divided into smaller and
smaller cells. Because the cytoplasm is clear, the spindle can be observed in real
time with a microscope. If the spindle is tugged into a new position with a fine
glass needle in early anaphase, the incipient cleavage furrow disappears, and a
new one develops in accord with the new spindle site—supporting the idea that
signals generated by the spindle induce local furrow formation.
How does the mitotic spindle specify the site of division? Three general mechanisms
have been proposed, and most cells appear to employ a combination of
these (Figure 17–45). The first is termed the astral stimulation model, in which the
actin filament
formation
myosin
phosphatase
regulatory myosin
light-chain
phosphorylation
myosin II activation
assembly and contraction of actin–myosin ring
Figure 17–44 Regulation of the
contractile ring by the GTPase RhoA.
Like other Rho family GTPases, RhoA
is activated by a RhoGEF protein and
inactivated by a Rho GTPase-activating
protein (RhoGAP). The active GTPbound
form of RhoA is focused at the
future cleavage site. By binding formins,
MBoC6 m17.52/17.44
activated RhoA promotes the assembly of
actin filaments in the contractile ring. By
activating Rho-activated protein kinases,
such as Rock, it stimulates myosin II
filament formation and activity, thereby
promoting contraction of the ring.