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Calcium Pumps in Health and Disease

Brini, Marisa, Carafoli, Ernesto·2009·Physiological Reviews

DOI 10.1152/physrev.00032.2008

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Abstract

Ca 2+-ATPases (pumps) are key actors in the regulation of Ca 2+in eukaryotic cells and are thus essential to the correct functioning of the cell machinery. They have high affinity for Ca 2+and can efficiently regulate it down to very low concentration levels. Two of the pumps have been known for decades (the SERCA and PMCA pumps); one (the SPCA pump) has only become known recently. Each pump is the product of a multigene family, the number of isoforms being further increased by alternative splicing of the primary transcripts. The three pumps share the basic features of the catalytic mechanism but differ in a number of properties related to tissue distribution, regulation, and role in the cellular homeostasis of Ca 2+. The molecular understanding of the function of the pumps has received great impetus from the solution of the three-dimensional structure of one of them, the SERCA pump. These spectacular advances in the structure and molecular mechanism of the pumps have been accompanied by the emergence and rapid expansion of the topic of pump malfunction, which has paralleled the rapid expansion of knowledge in the topic of Ca 2+-signaling dysfunction. Most of the pump defects described so far are genetic: when they are very severe, they produce gross and global disturbances of Ca 2+homeostasis that are incompatible with cell life. However, pump defects may also be of a type that produce subtler, often tissue-specific disturbances that affect individual components of the Ca 2+-controlling and/or processing machinery. They do not bring cells to immediate death but seriously compromise their normal functioning.

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Authors: Brini, M., & Carafoli, E.
Venue: Physiological Reviews
Publisher: American Physiological Society
Published: 2009-10
Volume: 89
Issue: 4
Pages: 1341-1378
ISSN: 0031-9333 (ISSN-L)
1522-1210
DOI: 10.1152/physrev.00032.2008
OpenAlex: W2136412900
Cited by: 676
References: 262
FWCI: 3.98
Type: journal article
Language: en
Open access: closed

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Calcium Pumps in Health and Disease

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