Prestin forms tetramer with each subunit being mechanically independent

作     者：WANG Xiang 1, GUO Wei-wei 2, HE David Zhi-Zhou1, YANG Shi-Ming 2 1 Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA 2 Institute of Otolaryngology, Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853 

作者机构：Department of Biomedical Sciences Creighton University School of Medicine Omaha NE 68178 USA Institute of Otolaryngology Department of Otolaryngology Head and Neck Surgery Chinese PLA General Hospital Beijing 100853 

出 版 物：《Journal of Otology》 (中华耳科学杂志（英文版）)

年 卷 期：2009年第4卷第2期

页      面：86-97页

学科分类：1003[医学-口腔医学] 1002[医学-临床医学] 100213[医学-耳鼻咽喉科学] 10[医学] 

基　　金：supported by an NIDCD grant (R01DC004696) to DH by National Natural Science Foundation of China grants 30871398, 30730040 and 30628030 to SY and DH supported bygrant number G20RR024001 from the National Center for Research Resources 

主　　题：Prestin oligomer outer hair cells electromotility nonlinear capacitance gerbil 

摘      要：Prestin is the motor protein of cochlear outer hair cells （OHCs）. It is able to perform rapid and reciprocal electromechanical conversion that underlies OHC electromotility. Due to the inadequate size of a single prestin molecule to form the2 nm intramembraneous protein particles （IMPs） in the OHC lateral membrane （LM）, the possibility of prestin oligomerization has been proposed. It has been suggested that prestin molecules form highorder oligomers, most likely as the tetramer, in heterologous systems. In OHCs, however, the oligomeric structure of prestin remains unclear. Here we calculated the prestin-related charge density in both gerbil and guinea pig OHCs through measuring their nonlinear capacitance （NLC） and LM surface area, showing that the average charge density （22, 608 μm-2 in gerbils; 19, 460 μm-2 in guinea pigs） is statistically 4 times the average density of IMPs （5,686 μm-2 in gerbils; 5, 000 μm-2 in guinea pigs）. This suggests that each IMP contains four prestin molecules based upon the notion that each prestin transfers a single elementary charge, implying that prestin forms tetramers in OHCs. To determine whether the prestin tetramer functions as a mechanical unit, we subsequently compared the slope factors （α） of electromotility and NLC simultaneously measured from the same OHC, showing that the α values of the two are statistically the same. This suggests that each prestin molecule in the tetramer is mechanically independent and equally contributes to OHC electromotility.