Current Biology Vol 20 No 4
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also organize the cortical actomyosin
cytoskeleton in syncytial structures,
i.e. the Drosophila embryo and, in the
case of ANI-2, the C. elegans oogenic
gonad.
Do anillins act early or late in
cytokinesis? Drosophila and
C. elegans anillins recruit septins
during contractile ring assembly.
Via septin recruitment, ANI-1 is
responsible for furrow asymmetry
throughout ingression in the
C. elegans zygote. Furrow initiation and
ingression occur with comparable
kinetics in C. elegans blastomeres
depleted of ANI-1. However, when
ANI-1 and Rho-kinase or ZEN-4
(the C. elegans MKLP1 homologue)
are simultaneously depleted,
cytokinesis is severely perturbed,
suggesting that the early functions
of anillins in cytokinesis can be
compensated by other proteins. In
contrast, human cells injected with
anti-anillin antibodies displayed
slow and abortive furrowing and,
consistent with this, the ingression
rate of the cellularization front is
slower in Drosophila anillin mutant
embryos. The idea that anillin’s
primary role is late in cytokinesis is
supported by the observations that,
in human and Drosophila cultured
cells depleted of anillin, the majority
of furrowing occurs normally, but
later in cytokinesis the actomyosin
cytoskeleton oscillates wildly along
the spindle axis, and cytokinesis
failure ensues.
How are anillins regulated?
S. pombe Mid1p is hyperphosphorylated
(probably by the Polo kinase Plo1p)
upon relocation from the interphase
nucleus to the cortex during
mitosis. Metazoan anillins are also
heavily phosphorylated, but the
kinase(s) responsible is not known.
In Drosophila and human cultured
cells, anillin recruitment to the
equatorial cortex depends on RhoA
activity, but is independent of other
cytoskeletal Rho downstream targets,
including Rho-kinase, myosin and
F-actin. Interestingly, post-anaphase
activation of Rho is itself dependent
on Polo kinase; thus, a parallel can be
drawn between metazoan and fission
yeast anillin regulation. After mitotic
exit, proteolysis of human anillin is
triggered by the anaphase-promoting
complex/cyclosome (APC/C).
S. pombe Mid2p is also regulated by
ubiquitin-mediated proteolysis,
indicating that its activity is actively
limited to cell division. Anillins can
be sequestered in the nucleus during
interphase, with the exceptions of
Drosophila anillin and C. elegans
ANI-1 in early embryos, ANI-2 in the
C. elegans oogenic gonad, and Mid2p
in fission yeast. Thus, some anillins
may regulate cytoskeletal dynamics
in contexts other than the cytokinetic
contractile ring.
Is anillin implicated in any
diseases? Because it is essential
for cell division, anillin is critical
for development and homeostasis
in metazoans. Anillin expression
levels correlate with metastatic
potential of human tumors from many
different tissue origins. Inhibition
of anillin expression suppressed
the growth of lung cancer cells in
culture. Considering that human
anillin is normally degraded after
mitotic exit and sequestered in
the nucleus during interphase, its
overexpression may overwhelm
these normal regulatory mechanisms,
freeing anillin to have an impact
on the actomyosin cytoskeleton
during events besides cytokinesis,
including, for example, cell motility,
and thus directly contribute to cancer
progression.
Where can I find out more?
D’Avino, P.P. (2009). How to scaffold the
contractile ring for a safe cytokinesis – lessons
from Anillin-related proteins. J. Cell Sci. 122,
1071–1079.
Field, C.M., and Alberts, B.M. (1995). Anillin, a
contractile ring protein that cycles from the
nucleus to the cell cortex. J. Cell Biol. 131,
165–178.
Hall, P.A., Todd, C.B., Hyland, P.L., McDade, S.S.,
Grabsch, H., Dattani, M., Hillan, K.J., Russell,
S.E. (2005). The septin-binding protein anillin
is overexpressed in diverse human tumors.
Clin. Cancer Res. 11:6780–6786.
Hickson, G.R.X. and O’Farrell, P.H. (2008). Anillin: a
pivotal organizer of the cytokinetic machinery.
Biochem. Soc. Trans. 36, 439–441.
Maddox, A.S., Habermann, B., Desai, A. and
Oegema, K. (2005). Distinct roles for two
C. elegans anillins in the gonad and early
embryo. Development 132, 2837–2848.
Maddox, A.S., Lewellyn, L., Desai, A., and
Oegema, K. (2007). Anillin and the septins
promote asymmetric ingression of the
cytokinetic furrow. Dev. Cell 12, 827–835.
1Cytoskeletal Dynamics and Cell Division
Laboratory, Institute of Research in
Immunology and Cancer, Université de
Montréal, C.P. 6128, Succ Centre- ville
Montréal, QC Canada H3C 3J7.
2Département de Pathologie et de
Biologie Cellulaire, Université de Montréal,
C.P. 6128, Succ Centre-ville Montréal, QC
Canada H3C 3J7.
*E-mail: [email protected]
Working memory
Alan Baddeley
Working memory refers to the system
or systems that are assumed to be
necessary in order to keep things in
mind while performing complex tasks
such as reasoning, comprehension
and learning. Over the last 30 years,
the concept of working memory
has been increasingly widely used,
extending from its origin in cognitive
psychology to many areas of
cognitive science and neuroscience,
and been applied within areas
ranging from education, through
psychiatry to paleoanthropology.
The term working memory was
coined in 1960 by Miller, Galanter and
Pribram in their classic book ‘Plans
and the Structure of Behaviour’, used
in 1968 by Atkinson and Shiffrin in
an influential paper [1], and adopted
as the title for a multicomponent
model by Baddeley and Hitch [2].
It is this use of the term that will
concern the rest of the discussion.
It is important to note, however,
that the term working memory was
adopted independently by Olton [3]
in connection with the performance
of animals, typically rats, in a multi-
arm radial maze in which each arm
was baited: the animals were given
several trials per day and needed to
remember which arm had already
been visited on that day, in order to
maximise reward. Within the human
context, this would be regarded as a
long-term memory task, demanding
more than the brief limited capacity
system that is assumed to comprise
human working memory. Olton’s
concept is still sometimes used in
studies based on animals, although
primate studies typically use the
term in the same way as it is used
in studies on humans.
This concept of working memory
evolved from that of short-term
memory, the temporary storage of
small amounts of material over brief
periods of time. It became a topic
of major interest during the 1960s,
linked to an information-processing
approach to psychology, in which
the digital computer served as a
theoretical basis for the development
of psychological theories. This
Primer
