Sensory Neurology

In my Sensory Neurology class I was asked to analyze a paper that paper aimed to demonstrate cadherin-23 and protocadherin-15 interact to form the tip links in sensory hair cells. More specifically that tip links are adhesion complexes consisting of CDH23 and PCDH15 and interact at .1mM Ca2+. What is known about tip links is that they are extracellular filaments that connect stereocilia to one another and allow for mechanotransduction to take place. They connect to cation-selective transduction channels that allow K+ and Ca2+ to enter the hair cell. There they have the ability to be deflected which allows for depolarization to take place. What these tiplinks were made of was unknown until this recent hypothesis. Skeptics say the development of the hair bundle is much more complex. Hearing loss and lack of mechanotransduction in a CDH23 mutant animal does not necessarily prove direct involvement of CDH23 in mechanotransduction. There is a possibility that the hair bundle itself has a different mutation or development issue that does not allow mechanotransduction to take place in the first place or that a particular mutation or change in one of the CDH23 domains affects a particular pathway that has a downstream effect on the actual tiplink.