Hearing and balance depend on sensory hair cells equipped with mechanosensitive, microvilli-like organelles, called stereocilia, that are capable of detecting displacements on a nanometer scale through mechanically gated channels located at their tips. Mammalian auditory hair cells are terminally differentiated and do not regenerate. While their stereocilia are exquisitely sensitive to mechanical vibration, orderly structured, and easily damaged by over-stimulation, they are maintained in proper working order for a lifetime. Each stereocilium is supported by a rigid paracrystalline array of several hundred parallel, uniformly polarized and regularly cross-linked actin filaments. The actin filaments are oriented such that the plus (barbed) ends are at the tips of the stereocilia and the minus (pointed) ends at the base. This organization of actin shares many construction principles with the actin formations in microvilli and filopodia yet can be up to 120?m in length. How such ordered actin formations are built, regulated, and renewed is largely unknown. We have now demonstrated that the seemingly static actin paracrystal at the core of sensory stereocilia of hair cells, undergoes continuous renewal enabled by reproducing itself at the stereocilia tips, treadmilling rearwards, and dismantling itself at the base. Treadmilling is a dynamic behavior of actin filaments that plays a crucial role in various forms of cell motility. However, little is known about the occurrence and regulation of this process in non-motile actin assemblies. We show that treadmill rates are scaled to the length of stereocilia and are modulated by local physical parameters, such as tension on the encapsulating membrane and on stereocilia links, as well as by myosins located at the tips and alongside the actin paracrystal. We propose that this regulated treadmilling dynamically shapes the functional architecture of stereocilia and plays a central role in recovery from over-stimulation. Such a dynamic view of a paracrystalline actin ensemble highlights how well organized cellular structures can maintain steady state structure, self-adjustment, and repair while undergoing continuous self-renewal.
Showing the most recent 10 out of 74 publications
