Pcdh15
Developmental stage
Highest level of expression is detected at embryonic day 16. Alternative splicing isoforms have different spatiotemporal expression patterns. In cochlear cultures at the equivalent of postnatal day 3, isoforms belonging to the CD1 (isoforms 1 through 9) and CD3 (isoforms 18 through 20) groups are highly expressed in hair bundles in the basal coils and moderately in those in the middle of the apical coil; they are hardly detectable in those at the apical end of the apical coil (at protein level). At the base of the cultured cochlea, in the more mature hair bundles, CD3 group isoforms are restricted to the tips of the shorter stereocilia in both inner and outer hair cells. By contrast, at the same stage, isoforms belonging to the CD2 group (isoforms 10 through 17) are highly expressed in hair bundles in the apex of the cochlea and, at lower levels, in those in the middle of the apical coil; they are hardly detectable at the base of the cochlea (at protein level). In mature hair bundles, CD1 group isoforms are distributed fairly evenly along most of the length of the stereocilia on auditory hair cells, whereas they are concentrated toward the upper third of the hair bundle in vestibular hair cells. In both the auditory and the vestibular organs, these isoforms are excluded from a region at the very tip of each stereocilium (at protein level). In contrast, CD2 group isoforms are undetectable in adult cochlear hair cells (at protein level). These isoforms are expressed in the entire hair bundle of the immature cells in the sensory epithelium of the early postnatal vestibule and only in the kinocilium in the more mature hair bundles (at protein level). CD3 group isoforms are detected in immature vestibular hair bundles, concentrated toward the tip of each stereocilium, as early as 15.5 dpc. They also localize to the tips of the shorter stereocilia in the mature vestibular hair bundles and are not detected at the tips of the stereocilia in the tallest row (at protein level).
Domain
Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with CDH23.
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.
Function
Calcium-dependent cell-adhesion protein. Required for inner ear neuroepithelial cell elaboration and cochlear function. Probably involved in the maintenance of normal retinal function.
Involvement in disease
Defects in Pcdh15 are the cause of the Ames waltzer (av) phenotype. It is characterized by deafness and a balance disorder, associated with the degeneration of inner ear neuroepithelia.
Tissue Specificity
Expressed in brain and sensory epithelium of the developing inner ear. Expressed in the retina, in the photoreceptor inner segments, the outer plexiform layer, the inner nuclei layer and the ganglion cell layer and, more diffusely in the inner plexiform layer (at protein level). Not detected in the retinal pigment epithelium (at protein level). Expressed in the spleen, dorsal root ganglion, dorsal aspect of neural tube, floor plate and ependymal cells adjacent to the neural canal.
Cellular localization
- Cell membrane
- Single-pass membrane protein
- Efficient localization to the plasma membrane requires the presence of LHFPL5.
- Isoform 1
- Cell membrane
- Single-pass type I membrane protein
- Isoform 2
- Cell membrane
- Single-pass type I membrane protein
- Isoform 3
- Secreted
- Isoform 4
- Cell membrane
- Single-pass type I membrane protein
- Isoform 5
- Cell membrane
- Single-pass type I membrane protein
- Isoform 6
- Cell membrane
- Single-pass type I membrane protein
- Isoform 7
- Cell membrane
- Single-pass type I membrane protein
- Isoform 8
- Cell membrane
- Single-pass type I membrane protein
- Isoform 9
- Cell membrane
- Single-pass type I membrane protein
- Isoform 10
- Cell membrane
- Single-pass type I membrane protein
- Isoform 11
- Cell membrane
- Single-pass type I membrane protein
- Isoform 12
- Cell membrane
- Single-pass type I membrane protein
- Isoform 13
- Secreted
- Isoform 14
- Secreted
- Isoform 15
- Secreted
- Isoform 16
- Secreted
- Isoform 17
- Secreted
- Isoform 18
- Cell membrane
- Single-pass type I membrane protein
- Isoform 19
- Cell membrane
- Single-pass type I membrane protein
- Isoform 21
- Secreted
- Isoform 22
- Secreted
- Isoform 23
- Secreted
Alternative names
Protocadherin-15, Pcdh15