The plasma membrane calcium pump in the hearing process:physiology and pathology

作     者：Ernesto CARAFOLI 

作者机构：Venetian Institute of Molecular MedicineUniversity of Padova 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2011年第54卷第8期

页      面：686-690页

核心收录：

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

主　　题：calcium ATPases PMCA2 hereditary deafness calmodulin hair cells 

摘      要：Mammalian cells express four different plasma membrane Ca2+ *** of them(PMCA1 and PMCA4) are expressed ubiquitously,and are considered housekeeping ***(PMCA2 and PMCA4) have tissue restricted *** are abundantly expressed in the brain and in nervous tissue-derived cell *** primary transcripts of all PMCAs undergo alternative splicing,generating a large number of additional *** occurs at site A,in the N-terminal moiety of the pump,and at site C,within the C-terminal calmodulin binding domain:The pumps are canonical targets of calmodulin *** site C insertion leads to a truncation of the pump about 50 residues short of the original *** of the pumps(PMCA2) has special properties:It displays high activity even in the absence of the natural activator calmodulin,and has a particularly complex pattern of alternative splicing at both sites A and C.A variant of the PMCA2 pump containing an insert at site A and truncated C-terminally is the resident isoform of the pump in the stereocilia of hair cells of the inner *** exports Ca2+to the endolymph that bathes the stereocilia less efficiently than the full length,non-inserted PMCA2 *** proper functioning of hair cells demands the precise maintenance of the Ca2+balance between hair cells and the endolymph. Disturbances in the balance affect the process of mechano-electrical transduction,which depends on the ability of the stereo-ciliar bundle to deflect in response to sound *** tip links that organize the bundle are formed by the Ca2+binding pro-tein cadherin 23 and by protocadherin 15:Disturbances of the Ca2+binding by cadherin 23 and/or of the ability of the PMCA2 variant of the stereocilia to export Ca2+to the endolymph generate hearing loss *** phenotypes have now been described in mice and *** some cases they are linked to mutations of both cadherin 23 and the PMCA2 pump,but in other cases they may be generated by mutati