期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 35, 期 -, 页码 919-922出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST0350919
关键词
calcium pump; calcium regulation; calcium signalling; calmodulin; plasma-membrane Ca2+-ATPase (PMCA)
资金
- NIGMS NIH HHS [GM28835, R01 GM028835, R01 GM028835-25] Funding Source: Medline
- NINDS NIH HHS [R01 NS051769, R01 NS051769-01A1, NS51769] Funding Source: Medline
Plasma-membrane calcium pumps [PMCAs (plasma-membrane Ca2+-ATPases)] expel Ca2+ from eukaryotic cells to maintain overall Ca2+ homoeostasis and to provide local control of intracellular Ca2+ signalling. Recent work indicates functional versatility among PMCA isoforms, with specific pumps being essential for cochlear hair cell function, sperm motility, feedback signalling in the heart and pre- and post-synaptic Ca2+ regulation in neurons. The functional versatility of PMCAs is due to differences in their regulation by CaM (calmodulin), kinases and other signalling proteins, as well as to their differential targeting and retention in defined plasma membrane domains. The basis for this is the structural diversity of PMCAs. in mammals, four genes encode PMCA isoforms 1-4, and each of these has multiple variants generated by alternative RNA splicing. The alternatively spliced regions are intimately involved in the regulatory interactions and differential membrane localization of the pumps. The alternatively spliced C-terminal tail acts as an autoinhibitory domain by interacting with the catalytic core of the pump. The degree of inhibition and the kinetics of interaction with the major activator CaM differ between PMCA variants. This translates into functional differences in how PMCAs handle Ca2+ signals of different magnitude and frequency. Accumulating evidence thus demonstrates how structural diversity provides functional versatility in the PMCAs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据