Biomedical Engineering Reference
In-Depth Information
2006; Strutt, Warrington, & Strutt, 2011
). A third would be trapping of
proteins to a domain by binding to a target (
Strutt et al., 2011
). A fourth
possibility would be for the rate of diffusion of the protein to be regulated
spatially across the cell (
Griffin, Odde, & Seydoux, 2011
).
4.5. mRNA localization?
The data do not support the hypothesis for localized synthesis as
in situ
hybrid-
ization experiments have failed to show evidence for mRNA localization.
Further, in other systems, the localization of an mRNA is usually mediated
by sequences outside the coding region (see e.g.,
Ferrandon, Elphick,
Nusslein-Volhard, & St Johnston, 1994; Macdonald & Struhl, 1988
).
However, in fly PCP, fully functional transgenes encode mRNAs that lack
most of the 5
0
-and3
0
-untranslated regions (see, e.g.,
Krasnow&Adler, 1994
).
4.6. Directional trafficking and trapping
There is evidence supporting the involvement of both directed transport and
trapping in the asymmetric accumulation of PCP proteins. Uemura and col-
leagues have used
in vivo
confocal imaging to determine that Fz and Stan
preferentially traffic along the proximal distal axis of wing cells as opposed
to along the anterior-posterior axis (
Shimada et al., 2006
). They also pro-
vided evidence that the trafficking is along the web of apical microtubules
that show a proximal/distal bias (
Turner & Adler, 1998
). This bias in the
orientation of microtubules appears to be at least partially mediated by
the action of the
ds/ft
pathway. This may provide an explanation for the abil-
ity of the
ds/ft
pathway to bias
fz/stan
activity (
Harumoto et al., 2010
). It is
not clear, however, if the bias for movement along the proximal distal axis is
great enough to explain everything. Further, the
in vivo
observations showed
that Fz-containing puncta could fuse with accumulations on the membrane
and that this appeared to be reversible (
Shimada et al., 2006; Strutt et al.,
2011
). Recent results of
Strutt et al. (2011)
obtained by FRAP
experiments established that the three transmembrane proteins Fz, Stan,
and Vang are all required for the stable asymmetric accumulation of PCP
protein complexes and that the cytoplasmic proteins Dsh, Pk, and Dgo
are needed for the formation of large puncta. The cytoplasmic proteins
could be recruited to the proximal and distal domains by interacting with
the complexes of transmembrane domains leading to further stabilization
and an increase in the size of the complexes. Consistent with that
possibility, Dsh has been shown to bind to Fz (
Wong et al., 2003
) and Pk
has been shown to bind to Vang (
Bastock et al., 2003; Jenny et al., 2003
).
