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 |
|---|---|
| Pages (from-to) | 2680-2689 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 20 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2001 Jun 1 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
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Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2+/- mice. / Zhao, Xiao Song; Shin, DongMin; Liu, Lynne H.; Shull, Gary E.; Muallem, Shmuel.
In: EMBO Journal, Vol. 20, No. 11, 01.06.2001, p. 2680-2689.Research output: Contribution to journal › Article
TY - JOUR
T1 - Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2+/- mice
AU - Zhao, Xiao Song
AU - Shin, DongMin
AU - Liu, Lynne H.
AU - Shull, Gary E.
AU - Muallem, Shmuel
PY - 2001/6/1
Y1 - 2001/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035355380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035355380&partnerID=8YFLogxK
U2 - 10.1093/emboj/20.11.2680
DO - 10.1093/emboj/20.11.2680
M3 - Article
C2 - 11387203
AN - SCOPUS:0035355380
VL - 20
SP - 2680
EP - 2689
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 11
ER -