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- Title
Plasticity and adaptation of Ca<sup>2+</sup> signaling and Ca<sup>2+</sup>-dependent exocytosis in SERCA2<sup>+/-</sup> mice.
- Authors
Zhao, Xiao-Song; Min Shin, Dong; H. Liu, Lynne; Shull, Gary E.; Muallem, Shmuel
- Abstract
Darier's disease (DD) is a high penetrance, autosomal dominant mutation in the ATP2A2 gene, which encodes the SERCA2 Ca2+ pump. Here we have used a mouse model of DD, a SERCA2+/- mouse, to define the adaptation of Ca2+ signaling and Ca2+-dependent exocytosis to a deletion of one copy of the SERCA2 gene. The [Ca2+]i transient evoked by maximal agonist stimulation was shorter in cells from SERCA2+/- mice, due to an up-regulation of specific plasma membrane Ca2+ pump isoforms. The change in cellular Ca2+ handling caused ∼50% reduction in [Ca2+]i oscillation frequency. Nonetheless, agonist-stimulated exocytosis was identical in cells from wild-type and SERCA2+/- mice. This was due to adaptation in the levels of the Ca2+ sensors for exocytosis synaptotagmins I and III in cells from SERCA2+/- mice. Accordingly, exocytosis was ∼10-fold more sensitive to Ca2+ in cells from SERCA2+/- mice. These findings reveal a remarkable plasticity and adaptability of Ca2+ signaling and Ca2+-dependent cellular functions in vivo, and can explain the normal function of most physiological systems in DD patients.
- Publication
EMBO Journal, 2001, Vol 20, Issue 11, p2680
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/20.11.2680