N-terminal mediated homo-multimerization of prestin, the outer hair cell motor protein

¹ Yale
² Yale University Sch. of Med.

^* To whom correspondence should be addressed. E-mail: joseph.santos-sacchi{at}yale.edu.

Submitted on June 15, 2005
Revised on July 11, 2005
Accepted on 8 August 2005

	Abstract

The outer hair cell lateral membrane motor, prestin, drives the cell's mechanical response that underpins mammalian cochlear amplification. Little is know about the protein's structure-function relations. Here we provide evidence that prestin is a 10 transmembrane domain protein whose membrane topology differs from previous models. We also present evidence that both intracellular termini of prestin are required for normal voltage sensing, with short terminal truncations of either resulting in absent or modified activity, despite quantitative findings of normal membrane targeting. Finally, we show with FRET that prestin-prestin interactions are dependent on an intact N-terminus, suggesting that this terminus is important for homo-oligomerization of prestin. These domains that we have perturbed likely contribute to allosteric modulation of prestin via interactions among prestin molecules or possibly with other proteins, as well.

Key Words: FACS, FRET, capacitance, cochlea, outer hair cell

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