Biomedical Engineering Reference
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PCP signaling. These conflicting or incomplete results will hopefully be
resolved through further examination.
Recently, several core PCP proteins have been shown to localize to the
cilium or basal body, adding a further layer of complexity to this relationship.
The membrane covering the protruding cilium is continuous with the cell
membrane, and several recent studies have demonstrated that numerous
molecules are trafficked onto the ciliary membrane ( Bloodgood, 2012 ).
In particular, Fat4 and Vangl2 have been detected on some ciliary mem-
branes and, as discussed, mutations in both genes cause PCP phenotypes,
including defects in stereociliary bundle orientation ( Saburi et al., 2008 ).
In addition, Vangl2 and Dvl have also been reported to associate with basal
bodies. Dvl acts to dock basal bodies to the apical membrane preceding
ciliogenesis ( Park et al., 2008 ), while Vangl2 has been shown to be respon-
sible for asymmetric positioning of motile cilia ( Borovina, Superina, Voskas,
& Ciruna, 2010 ). Moreover, a recent proteomic screen found several PCP-
associated proteins in the human centrosome such as PRICKLE3, SCRIB,
CCDC66, and ALBATROSS ( Jakobsen et al., 2011 ). Finally, though not a
core PCP gene, Fritz controls localization of the cytoskeletal protein Septin,
crucial for collective cell movement and ciliogenesis in Xenopus embryos.
Although not a cilia protein per se , mutations in human FRITZ have been
identified in two ciliopathies, BBS and Meckel-Gruber syndrome ( Kim
et al., 2010 ).
Overall, these findings clearly implicate cilia and cilia-related proteins in
PCP signaling within the auditory system. However, the specific nature of
the interactions between cilia and the core PCP signaling cassette remains
unclear. Analysis of Ift88 and Kif3a mutants would suggest that positioning
of the kinocilium and its basal body is a downstream effect of PCP signaling.
But other data potentially place ciliary signaling upstream of, or parallel with,
the PCP cassette. The lumenal location of developing kinocilia puts them in
an excellent position to act as receptive antennae for extracellular signaling
cues ( May-Simera & Kelley, 2012 ), a role that has been confirmed for other
cilia by the recent localization of multiple receptor molecules on their surfaces
( Bloodgood, 2012 ). Further, the basal body, located at the base of the
kinocilium, is emerging as a regional signaling hot spot. Not only do numer-
ous signaling molecules localize to this region, but also activation and/or deg-
radation of signaling proteins occurs in this region. Additionally, the basal
body, which is derived from the mother centriole, acts as a microtubule
organizing center, which can regulate the nucleation and outgrowth of
intracellular microtubules ( Kim et al., 2004; May-Simera & Kelley, 2012;
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