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.
Original language | English |
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Pages (from-to) | 2680-2689 |
Number of pages | 10 |
Journal | EMBO Journal |
Volume | 20 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2001 Jun 1 |
All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)