cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
protocadherin subfamily
CATEGORY
adhesion
, receptor
membrane
SUBCELLULAR LOCALIZATION
plasma membrane,junction
intracellular
intracellular,nuclear envelope,int
text
integral plasma membrane,localized at the synaptic junction
expressed in photoreceptor cells of the mammalian retina, where it is colocalized with harmonin, myosin VIIa, and cadherin 23 at the synaptic terminal
basic FUNCTION
maintaining normal function of inner ear and retina
mediating adhesion in synaptic junctions through lack-in process
playing an essential role in maintaining the normal organization of the stereocilia bundle
CDH23, PCDH15 and ADGRV1 have been implicated in the development of cochlear hair cell stereocilia, while CLRN1 has been suggested to also play a role in synaptogenesis
USH1G, MYO7A, USH1C, CDH23, PCDH15 form an adhesion belt around the basolateral region of the photoreceptor outer segment, and defects in this structure cause the retinal degeneration in USH1 patients
PCDH15 and LHFPL5 facilitate each other’s cell surface transport
is a central component of the mechanotransduction complex in auditory and vestibular hair cells
is a core component of hair cell tip-links and crucial for proper function of inner ear hair cells
CELLULAR PROCESS
cell organization/biogenesis
PHYSIOLOGICAL PROCESS
development
PATHWAY
metabolism
signaling
signal transduction
, sensory transduction/hearing
cell-cell signaling
a component
TMIE forms a ternary complex with the tip-link component PCDH15 and its binding partner LHFPL5
INTERACTION
DNA
RNA
small molecule
metal binding,
Ca2+
protein
interacted with harmonin USH1C (probably play a role in disk morphogenesis)
interact CDH23 to form a filament with structural similarity to tip links, in sensory hair cells
CDH23 and PCDH15 interact to form tip links, which gate mechanotransduction channels in hair cells of the inner ear (Elledge 2010)
cytoplasmic N-terminus of HCN1 binds the cytoplasmic C-terminus of stereociliary tip-link protein PCDH15
is an integral component of the hair cells mechanotransduction machinery that functionally couples PCDH15 to the transduction channel
CDH23, PCDH15 bind tip-to-tip in a "handshake" mode that involves the EC1 and EC2 repeats ofCDH23, PCDH15
PCDH15 interacts with transmembrane channel-like proteins TMC1 and TMC2
both LHFPL5 and TMC1 were shown to interact with PCDH15, a component of the tip link, which applies force to the mechanotransducer (MT) channel
interaction of MYO3A with the cytosolic tail of the integral tip-link protein protocadherin 15 (PCDH15), a core component of MET complex
GOPC, a Golgi-associated, PDZ domain-containing protein, interacts with PCDH15
CDH23 and PCDH15, interact in a Ca2+-dependent manner to form tip links
in cytotoxic tumor-derived T- and NK-cell lines as well as in biopsies of nasal NK/T-cell lymphomas
Susceptibility
to familial combined hyperlipidemia
to Noise-induced hearing loss (NIHL)
Variant & Polymorphism
SNP
nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia (Huertas-Vazquez 2010)
genetic variations in PCDH15 modify the susceptibility to NIHL development
Candidate gene
Marker
Therapy target
ANIMAL & CELL MODELS
Ames waltzer a recessive mutation in mice causes deafness and a balance disorder associated with the degeneration of inner ear neuroepithelia
Digenic heterozygotes mice for cadherin 23 and protocadherin 15 display a significant levels of hearing loss, cytoarchitectural defects in the cochlea, degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells
Pcdh15-CD2-deficient mice are deaf, lack kinociliary links and have abnormally polarized hair bundles
noddy homozygotes lack inner ear function, and noddy mutant mice harbor an isoleucine-to-asparagine (I108N) mutation in the EC1 repeat of Pcdh15
