Biomedical Engineering Reference
In-Depth Information
domain and has sequence similarity to diaphanous family formins. These
formins are known to function as dimers, be activated by Rho:GTP, and
promote the formation of long actin filaments (
Campellone & Welch,
2011; Chesarone, DuPage, & Goode, 2011; Goode & Eck, 2007
).
Consistent with the sequence similarity between Mwh and Dia, both
genetic interactions and coimmunoprecipiation experiments argue that
Rho1 activates Mwh (
Yan et al., 2009
). This raises the possibility that
Mwh might
inhibit
the actin cytoskeleton by acting as a dominant
negative formin.
6.3. A distal target of Dsh?
The cytoskeleton is activated to form a hair in the vicinity of the distal most
vertex of pupal wing cells (
Wong & Adler, 1993
). The level of activity is im-
portant for insuring a singlehair is formed and that it is theproper size and shape.
For example, if the actin cytoskeleton is inhibited by drug treatment or bymu-
tations in actin cytoskeleton components such as myosin II, multiple shorter
than normal hairs are formed (
Franke, Montague, & Kiehart, 2010; Turner
& Adler, 1998
). Inhibition at the proximal side of wing cells from the
recruitment of Mwh seems insufficient to specify the distal vertex. Several
lines of data indicate that distal edge proteins can stimulate the cytoskeleton.
Although mutations in
in
,
fy
,
frtz
,and
mwh
are epistatic to loss-of-function
mutations in distal proteins such as
dsh
and
fz
that is not the case for all gain
of functions in those genes. The late overexpression of
dsh
leads to the
formation of multiple hair cells and an increase is seen even when cells also
lack
in
or
mwh
function (
Lee & Adler, 2002
). Indeed, the effects of these
two genetic changes are additive. Thus, at least when overexpressed Dsh is
able to affect cytoskeleton function and it must be doing so by interacting
with an unidentified cellular constituent and not known
fz/stan
downstream
components such as
in
or
mwh
. Independent evidence supporting the distal
edge proteins stimulating the cytoskeleton came from Strutt and colleagues
who found that Fz acted to promote hair formation (
Strutt & Warrington,
2008
). Several experimental results supported this idea including a delay in
hair initiation in
fz
mutant cells compared to wild-type neighbors. This was
seen even when comparing
fz
and
fz
รพ
cells in a
Vang
mutant background
where Fz was not properly localized.
The identity of the putative distal target(s) is currently unknown. In
principle, the target could be a cytoskeletal activator that is activated by
the distal proteins or, alternatively, a cytoskeletal
inhibitor
that
is
