THESIS
2019
ix, 94 pages : illustrations (some color) ; 30 cm
Abstract
The mechanoelectrical transduction (MET) channel in auditory hair cells transduces mechanical stimuli (sound waves) into electrical signals, which is indispensable in the mammalian hearing process. Yet its molecular identity remains unclear. Transmembrane channel-like (TMC) protein 1 is proposed to be the pore-forming subunit of MET channel. To decipher the function of TMC1 in mechanotransduction and to search for other proteins working together in the mechanotransduction machinery, we studied the function of TMC1 when ectopically expressed in mammalian cell lines and screened the potential binding partners of TMC1.
Here we identify Rab37, a small GTPase with a reported function of facilitating exocytosis of several important proteins, as a binding partner of TMC1. Rab37 binds to and u...[
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The mechanoelectrical transduction (MET) channel in auditory hair cells transduces mechanical stimuli (sound waves) into electrical signals, which is indispensable in the mammalian hearing process. Yet its molecular identity remains unclear. Transmembrane channel-like (TMC) protein 1 is proposed to be the pore-forming subunit of MET channel. To decipher the function of TMC1 in mechanotransduction and to search for other proteins working together in the mechanotransduction machinery, we studied the function of TMC1 when ectopically expressed in mammalian cell lines and screened the potential binding partners of TMC1.
Here we identify Rab37, a small GTPase with a reported function of facilitating exocytosis of several important proteins, as a binding partner of TMC1. Rab37 binds to and upregulates TMC1 in vitro, and colocalizes with TMC1 in the stereocilia of mouse auditory hair cells. The expression pattern of Rab37 in mouse hair cells changes during development. Moreover, expression level of Rab37 in the mouse cochlea is boosted after LPS-induced inflammation. Rab37
-/- mouse was generated to test the hearing function of Rab37 in vivo.
Rab37
-/- mouse has no overt hearing impairment in normal condition but shows increased sensitivity to noise exposure. Our work identifies Rab37 as a novel binding partner of TMC1 and demonstrates Rab37’s potential function in regulating the function of TMC1.
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