The overall goal of the project is to define and characterize the organelles and specialized molecular
machinery for protein assembly, processing and transport in hair cells, and the defects in this process that
cause deafness. We propose here to investigate the mechanisms by which TOMT regulates transport of a
subset of functionally important proteins in hair cells, and to begin to uncover TOMT-associated proteins that
participate. Based on our preliminary data, we hypothesize that TOMT is an endoplasmic reticulum protein that
is critical for assembly and transport of a specific set of transmembrane proteins in hair cells. To test our
hypothesis, we will: i) use immunolocalization and immunogold transmission electron microscopy to precisely
localize TOMT to hair-cell specific transport organelles; ii) identify and characterize important TOMT functional
domains; and iii) look for interaction partners for TOMT that functionally cooperate in hair cell protein transport.
Our preliminary data show the feasibility of our approach. We anticipate that our studies will elucidate new
insights into the unique molecular machinery of hair cell protein transport that establishes distinctive functional
specializations critical for auditory processing. Furthermore, a better understanding of protein transport
mechanisms in hair cells has the potential to provide important context for protein transport deficits that are
common in hearing loss.