Cell News 3/2013
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stratum spinosum
stratum basale
stratum granulosum
stratum corneum
?
Tight Junction
Desmosome
Hemidesmosome
Adherens Junction
SCRIB
DLG1
LGL1/2
PALS1
Crumbs
Lin7
PATJ
Par3
Par6
aPKC
Par1
Par4
AJ
apical
basolateral
basal
A
B
RESEARCH NEWS
the stratum corneum. This process requires intercellular rear-
rangements to allow cells to migrate through the layers. Ano-
ther example of polarity is oriented cell division of basal cells
in the IFE and in hair follicles. By orienting the mitotic spindle
either parallel (symmetric cell division, SCD) or perpendicular
(asymmetric cell division, ACD) with respect to the underlying
basement membrane, stem and progenitor cells can control cell
fate while guaranteeing renewal (Fig.2B). Wound closure is a
highly polarized process that requires the coordinated secretion
and deposition of extracellular matrix to allow for directional
migration of keratinocytes. Cilia are positioned in a polarized
manner on keratinocytes and this is likely important for their
role in signal transduction. Not only individual cells or subcel-
lular structures are highly polarized but the orientation of mul-
ticellular structures such as sebaceous glands and hair follicles
are organized in the plane of the tissue. All of these processes
depend on cell and tissue polarity and work by several groups
including ours have started to unravel how polarity genes con-
tribute to these processes in stratifying epithelia.
The atypical protein kinase C: a key regulator of
polarity
Atypical protein kinase C (aPKC) is a serine/threonine kinase
that has emerged as an evolutionary conserved central regulator
of all forms of polarity and thus of cell and tissue architecture
in almost all cell types (Suzuki and Ohno, 2006; Goldstein and
Macara, 2007). aPKC binds the scaffolding proteins Par6 and
Par3 to form the Par3/Par6/aPKC polarity complex. Par6 regu-
lates aPKC kinase activity whereas Par3 can function both as
an upstream regulator and downstream effector of aPKC and
may have independent functions outside of the complex (Gold-
stein and Macara, 2007). By coupling to different downstream
interaction partners or substrates this complex drives the asym-
metric distribution of proteins and thus functional activity. For
example, by coordinating the establishment of apical membrane
identity and the formation and positioning of barrier forming
tight junctions, which separate apical from basolateral mem-
branes, aPKC regulates the proper function of simple epithelial
ion and size barriers that separate tissues (Suzuki and Ohno,
2006). The aPKC/Par complex has also been implicated in the re-
gulation of insulin/IGF and NF
κ
B signaling (Moscat et al., 2009)
and may thus couple control of cyto-architecture to the regu-
lation of metabolism and inflammation (Martin-Belmonte and
Perez-Moreno, 2012).
Atypical PKCs belong to the protein kinase C family of cytosolic
serine and threonine kinases. Unlike the other members of this
family, atypical PKCs are not activated by either phorbol es-
ters or Ca
2+
due to the lack of binding motifs. In mammals two
isoforms of aPKC exist, aPKCzeta (aPKC
ζ
) and aPKCiota/lamb-
da (aPKC
ι/λ
), which are highly related but encoded by separa-
te genes (reviewed in Rosse et al., 2010). In vitro studies have
implicated both aPKCs in the regulation of polarity. However,
complete inactivation of aPKC
ζ
resulted in viable mice with re-
duced B-cell survival and altered NFkB signaling (Leitges et al.,
2001) whereas aPKC
λ
knockout mice die early during embryo-
genesis due to gastrulation defects (Soloff et al., 2004; Seidl et
al., 2013). This suggests separate functions for the two isoforms
Figure 1. Functional similarities and differences of polarity in simple epithelia and stratifying epithelia.
At present it is unclear if the same molecular mechanisms controlling apico-basal polarity in simple epithelia are involved in the establishment of epider-
mal polarity (question mark). (A) Apico-basal polarity in simple epithelia. The apical junctional complex, consisting of tight junctions (TJ) and adherens
junctions (AJ) forms a border to establish apico-basal polarity. Mutual interactions between polarity proteins and complexes regulate apico-basal polarity
and barrier formation in simple epithelia. (B) Polarity in the murine epidermis. In contrast to simple epithelia, the epidermis has no distinct apical and ba-
solateral membrane domains, but displays apico-basal polarity from the stratum basale as the most basal layer and the stratum spinosum to the stratum
granulosum forming the viable apical border and the stratum corneum, the outermost dead water impermeable layer. Polarity in this multilayered tissue
is also reflected in cell shapes and adhesive junctions. Moreover, lamellar bodies (blue circles) and keratohyalin granules (purple asterisks) are targeted
(indicated by arrows) towards the upper layers to form the cornified envelope.
