(A and B) In a recent model, the upper end of the tip link connects directly or indirectly (not shown) with the mechanoelectrical transduction (MET) channel(s). Slow adaptation involving the [Ca2+]i-dependent climbing and sliding of myosin motors is indicated by the arrows.
(C) A revised model taking into account the transmembrane proteins PCDH15 and CDH23. Major building blocks of the upper tip-link density (UTLD) are harmonins, which provide a sturdy anchor point for the tip link with the cytoskeleton. MET channels have recently been shown to be associated with the lower tip-link density (LTLD), but their mechanical link to the lower insertion point of the tip link is unclear (question mark). Tenting of the membrane, however, would be consistent with activation by membrane stretch.
(D) In dfcr mutant mice, harmonin is absent from the upper tip link insertion point, affecting the transduction apparatus’ mechanical characteristics. It is not clear whether other proteins (indicated in turquoise) that have been proposed in this region are affected.