The tip link sits at the business end of a hair cell, linking the top of a shorter stereocilia on the hair bundle to its taller neighbor, and thus presumably gating the mechanosensitive channels. This week, Ahmed et al. set out to identify the protein previously known as the tip-link antigen (TLA). Using mass spectrometric analysis of TLA, the authors identified TLA as protocadherin-15. The isoforms of protocadherin-15 had distinct C-terminal domains (CD1, CD2, and CD3). The distribution of two of the isoforms suggested that they are part of the tip-link complex, probably serving as anchoring elements rather than the central strand. Protocadherin-15-CD3 immunoreactivity was found at the basal end where the tip link attaches to the shorter stereocilia, and CD1 immunoreactivity was found at the distal end where the tip link attaches to the taller sterocilium. Calcium chelation, known to remove tip links and abolish mechanotransduction, also caused loss of CD3 immunoreactivity. #### Tips from The Journal of Neuroscience Zubair M. Ahmed, Richard Goodyear, Saima Riazuddin, Ayala Lagziel, P. Kevin Legan, Martine Behra, Shawn M. Burgess, Kathryn S. Lilley, Edward R. Wilcox, Sheikh Riazuddin, Andrew J. Griffith, Gregory I. Frolenkov, Inna A. Belyantseva, Guy P. Richardson, and Thomas B. Friedman Contact: Sara Harris Society for Neuroscience (责任编辑:泉水) |