compartments, Fzd6 and Vangl2
are found on distinct vesicular
compartments in vivo, indicating that
antero-posterior core PCP asymmetry
is preserved during mitosis. How is this
endosomal asymmetry maintained?
Devenport et al.  report that, in
cultured keratinocytes, mitotically
internalized Celsr1 colocalizes with
various endocytic markers, including
Rab5- and EEA1-positive early
endosomes, Rab11-positive recycling
endosomes, as well as caveolin .
This observation raises the possibility
that anterior and posterior cognate
PCP complexes could follow distinct
endocytic routes to be targeted to
distinct classes of endosomes, thereby
preventing the different PCP
complexes from mixing in mitosis.
During cytokinesis, Celsr1-positive
compartments are distributed in
a polarized manner at the anterior
and posterior poles of daughter cells
(Figure 1C). Strikingly, endosomal
vesicles are shown to interpret
antero-posterior cues independently
of mitotic spindle orientation. Stunning
mosaic experiments revealed that,
at this stage, polarisation of the
Celsr1-positive endosomes is dictated
in a cell-non-autonomous manner
by the interphasic neighboring
PCP-polarized cells . Whether
and how endosomes containing the
anterior or posterior PCP complex
selectively recognize and fuse with
the respective cognate anterior or
posterior cortex remains unknown.
It will also be interesting to understand
how polarized endosomal recycling
drives PCP re-establishment at the
boundaries of the two daughter cells
(Figure 1D). In addition, future studies
will assist our understanding of how
PCP complexes from neighboring
interphasic cells are maintained at the
boundaries of mitotic cells.
What are the underlying molecular
mechanisms and the biological
relevance of selective mitotic
internalization? Using a series of
domain swapping and point mutation
experiments, Devenport et al.  reveal
that a single juxtamembrane di-leucine
signal present in the cytoplasmic
domain of Celsr1 is necessary to
promote its mitotic internalization.
Importantly, in clones of cells
expressing the endocytic-defective
version of Celsr1, hair follicles are
no longer aligned along the
antero-posterior axis. Mutant cells
align one relative to the other,
a misorientation that is transmitted
in a dominant cell-non-autonomous
manner to adjacent wild-type cells .
These observations first strongly argue
that mitotic internalization of PCP
components is physiologically
important and second lead to the
proposal that mitotic uptake occurs
to prevent PCP signaling from the
rounded cell, therefore avoiding
disruption of PCP by aberrant
directional information. Is this
mechanism evolutionarily conserved?
Perhaps not, given that mitotic
internalization of PCP components has
not been reported in Drosophila [17,18]
and mitotic internalization motif of
Celsr1 is not conserved in dipters .
How then is PCP transmitted in
daughter cells inthefly?Clearly, further
investigation of mitotic endocytosis
of PCP components in model systems
will provide new and exciting insights
into how polarized trafficking allows
inheritance of PCP in tissues.
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CNRS, UMR 6061, Institut Ge ´ne ´tique
et De ´veloppement de Rennes, Universite ´
Rennes 1, UEB, IFR 140, F-35043 Rennes,
Protein Degradation: BAGging Up the
Cells efficiently uncover and degrade proteins that are misfolded. However, we
know very little about what cells do to protect themselves from mislocalized
proteins. A new study reveals a novel quality control pathway that recognizes
and degrades secretory pathway proteins that have failed to target to the
Tslil Ast and Maya Schuldiner*
Have you ever had the dubious
pleasure of finding groceries that
you’ve forgotten to place in the
refrigerator? Holding your breath and
looking away, the only thing left to do is
to promptly throw everything out. In
Current Biology Vol 21 No 18