Cadherin 23 is a component of the transient lateral links in the developing hair bundles of cochlear sensory cells.
Cadherin 23 is required for normal development of the sensory hair bundle, and recent evidence suggests it is a component of the tip links, filamentous structures thought to gate the hair cells' mechano-electrical transducer channels. Antibodies against unique peptide epitopes were used to study the properties of cadherin 23 and its spatio-temporal expression patterns in developing cochlear hair cells. In the rat, intra- and extracellular domain epitopes are readily detected in the developing hair bundle between E18 and P5, and become progressively restricted to the distal tip of the hair bundle. From P13 onwards, these epitopes are no longer detected in hair bundles, but immunoreactivity is observed in the apical, vesicle-rich, pericuticular region of the hair cell. In the P2-P3 mouse cochlea, immunogold labeling reveals cadherin 23 is associated with kinocilial links and transient lateral links located between and within stereociliary rows. At this stage, the cadherin 23 ectodomain epitope remains on the hair bundle following BAPTA or La(3+) treatment, but is lost following exposure to the protease subtilisin. In contrast, mechano-electrical transduction is abolished by BAPTA but unaffected by subtilisin. These results suggest cadherin 23 is associated with transient lateral links that have properties distinct from those of the tip-link.
Michel
Vincent
V
Unité de Génétique des Déficits Sensoriels, INSERM U587, Institut Pasteur, Paris, France.
Goodyear
Richard J
RJ
Weil
Dominique
D
Marcotti
Walter
W
Perfettini
Isabelle
I
Wolfrum
Uwe
U
Kros
Corné J
CJ
Richardson
Guy P
GP
Petit
Christine
C
D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D003051:Cochlea / Q000196:embryology*; D003593:Cytoplasm / Q000378:metabolism; D007758:Ear, Inner / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000939:Epitopes / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000196:embryology*; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000494:pharmacology; D007811:Lanthanum / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008957:Models, Genetic; D017434:Protein Structure, Tertiary; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020860:Subtilisin / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
D015820:Cadherins; C499091:Cdh23 protein, mouse; D000939:Epitopes; D007202:Indicators and Reagents; D004533:Egtazic Acid; D007811:Lanthanum; D020860:Subtilisin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid