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

Science China(Life Sciences) 2011年第8期54卷 686-690页

作者： ernesto carafoli Venetian Institute of Molecular Medicine University of Padova

Mammalian cells express four different plasma membrane Ca2+ ATPases.Two of them(PMCA1 and PMCA4) are expressed ubiquitously,and are considered housekeeping isoforms.Two(PMCA2 and PMCA4) have tissue restricted distribution.They are abundantly expressed in the brain and in nervous tissue-derived cell types.The primary transcripts of all PMCAs undergo alternative splicing,generating a large number of additional isoforms.Splicing 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 stimu-lation.The site C insertion leads to a truncation of the pump about 50 residues short of the original C-terminal.One 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 ear.It exports Ca2+to the endolymph that bathes the stereocilia less efficiently than the full length,non-inserted PMCA2 pump.The 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 waves.The 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.Such phenotypes have now been described in mice and humans.In some cases they are linked to mutations of both cadherin 23 and the PMCA2 pump,but in other cases they may be generated by mutations of particular severity in only one of the tw

关键词：细胞膜钙泵选择性剪接病理生理钙粘蛋白组织分布钙调蛋白

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Ca^(2+):a versatile master key for intracellular signaling cascades

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Science China(Life Sciences) 2011年第8期54卷 683-685页

作者： Shi-Qiang WANG Michael XZHU ernesto carafoli State Key Lab of Biomembrane and Membrane Biotechnology Peking University College of Life Sciences Beijing 100871 China Department of lntegrative Biology and Pharmacology the University of Texas Health Science Center at Houston Houston 77030 USA Venetian Institute of Molecular Medicine University of Padova Padova 35121 Italy

Ca2+is one of the most ancient and versatile intracellular messengers in both animal and plant systems.Ca2+interacts with a huge array of signaling proteins,and coordinates the integration of non-signaling proteins in... 详细信息

关键词：信号蛋白主密钥细胞内蜂窝移动通信系统通用 CA 级联植物系统

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