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Key to Lifelong Hearing Identified as Continuous Self-Renewal of the Sensory Stereocilia
Why do some people recover from some noise exposure in a matter of hours or days? Why, in fact, are humans able to make use of the mechanically-sensitive hair cell stereocilia to hear throughout the auditory punishments of a lifetime? Most mechanical systems, when assaulted, break down or cease to function.
According to Dr. Bechara Kachar and his colleagues at the National Institute on Deafness and Other Communication Disorders (NIDCD), Section on Structural Biology, "the answer to this rapid recovery appears to be centered in a "treadmill" of renewal, running from the tip of the sensory stereocilia to its base." The study (PDF; get Adobe Reader) is published in the 22 August issue of Nature.
Earlier, scientists had hypothesized that the stereocilia remained rigid because they were supported by a sturdy backbone made of a crystalline array of cross-linked parallel filaments composed of the protein actin. Actin is a robust protein.
NIDCD's investigators followed the preferential localization of a specific type of actin in the stereocilia to determine the locus of actin polymerization. Polymerization is a standard chemical process whereby individual molecules known as "monomers" self-associate to form large and often regular aggregates, like the naturally-occurring silkworm polymers. Using a fluorescent tag, a method used by molecular biologists to track newly synthesized proteins in the cell, these NIDCD scientists demonstrated that the sensory stereocilia of hair cells are continuously being renewed by a process driven by actin polymerization and treadmilling at the core of each stereocilia.
Although other scientists have identified these actin filament bundles as uniformly ordered in the stereocilia, "Dr. Kachar and his team have seen the remodeling of these filament bundles by addition of new actin monomers at the tips of the stereocilium and, for the first time, witnessed their renewal every 48 hours," notes James F. Battey, Jr., M.D., Director of the NIDCD.
The discovery, in an animal model closely related to human functioning, of this self-renewal has much broader implications, in that the stereocilium is one of group of cellular organelles that share a structural backbone of cross-linked parallel actin filaments formed into a dense semi crystalline filament bundle. Not only is this an astounding contribution to auditory and structural biological research, but it has direct implications for those who are studying similar cellular organelles including Drosophila's bristles, nurse cell struts, fertilization cones, and spermatozoa acrosomal structures.
The work described in this week's issue of Nature is being followed up with additional studies to determine how the stereocilia can counterbalance the downward movement of the treadmill. The team proposes that activity from myosins, mechano-enzymes capable of moving cargo along actin filaments would allow the membrane associated components of the stereocilia to remain structurally stable and ready for mechanical deflection. The limberness of the stereocilia is key to their ability to respond to deflection and provide precise information that is interpreted by the brain as the range of sound.
Dr. Kachar and his team have gained a clearer view of how hearing is maintained under normal circumstances. They have also been given new insight into the recovery of hearing after some instances of noise exposure as well as information that could help understand the molecular basis of several genetic, environmental and age-related inner ear disorders that involve either malformation or the disruption of stereocilia plasticity.