Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2+/- mice

Xiao Song Zhao, Dong Min Shin, Lynne H. Liu, Gary E. Shull, Shmuel Muallem

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62 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2680-2689
Number of pages10
JournalEMBO Journal
Issue number11
Publication statusPublished - 2001 Jun 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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