Upstream of Hippo signaling. The polarized architecture of epithelial cells depends on the highly stereotypic distribution of cellular junctions and
other membrane-associated protein complexes. In epithelial cells of the Drosophila embryo, 3 distinct domains
subdivide the lateral plasma membrane. The most apical one comprises the subapical complex. It is followed by the
zonula adherens, and, further basally, by the septate junction. A core component of the subapical complex is the
transmembrane protein crumbs, the cytoplasmic domain of which recruits the PDZ protein 'Discs Lost' into the
complex. Cells lacking crumbs or the functionally related gene 'stardust' fail to organize a continuous zonular adherens
and to maintain cell polarity.
NCBI Summary:
Mutations in this gene have been associated with a severe form of retinitis pigmentosa, RP12. The function of its protein product is unknown. Homology to the Drosophila gene crumbs suggests that the protein may be involved in neuronal development of the retina through cell-cell interactions.
General function
Cell adhesion molecule, Cytoskeleton organization
Comment
Human
CRUMBS protein is a predicted paracrine factor, establishing and maintaining cellular polarities. Crb1 expression in the
ovary is restricted to the oocytes in both preantral and antral follicles. Drosophila crumbs protein is an important factor in establishing and maintaining cellular polarity through interactions with
the cytoskeleton . Human CRB1 is highly conserved relative to Drosophila crb yet has splice variants that lead to
fundamentally different molecules. One transcript splice variant encoded by CRB1 is reduced in the transmembrane domain,
and the protein is probably secreted. The other splice variant includes the cytoplasmic domain and the transmembrane
region and is functionally identical to Drosophila crumbs.
A possible role for Crb1 in the mouse ovary is the
organization of the granulosa cells in the developing follicle Taft RA, et al 2002 . Granulosa cells can be seen as analogous to the follicular
epithelium in the Drosophila ovary but lack the highly defined apical/basal polarity. However, the granulosa cells do have
distinct morphologies that are developmentally regulated and may be under the control of the oocyte. CRUMBS protein is a
likely candidate for an element of the oocyte-granulosa cell regulatory loop.
Cellular localization
Secreted, Plasma membrane
Comment
Ovarian function
Follicle development
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Taft RA, et al 2002 reported the identification of genes encoding mouse oocyte secretory and
transmembrane proteins by a signal sequence trap.
At all stages of follicular
development, oocytes interact with surrounding granulosa cells and promote their
differentiation into the types of cells that support further oocyte growth and
developmental competence. These interactions suggest the existence of an
oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell
surface receptors on both cell types. Factors involved in the regulatory loop will
therefore contain a signal sequence, which can be used to identify them through a
signal sequence trap (SST). A screen of an oocyte SST library identified three
classes of oocyte-expressed sequences: known mouse genes, sequences homologous
to known mammalian genes, and novel sequences of unknown function. Many of the
recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For
several of the known mouse genes (e.g. Crumbs1), new roles in follicular development are implied
by identification of their expression, for the first time, in the oocyte.