cADPR stimulates SERCA activity in Xenopus oocytes

Area of Science:

• Cellular Physiology
• Molecular Biology
• Biochemistry

Background:

• Cyclic ADP-ribose (cADPR) is an intracellular second messenger known to release Ca(2+) via ryanodine receptors (RyRs).
• Potential modulation of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump activity by cADPR has been proposed but remains complex due to concurrent RyR actions.

Purpose of the Study:

• To investigate the role of cADPR in modulating Ca(2+) sequestration independently of RyR activity.
• To elucidate the specific effects of cADPR on SERCA pump function in Xenopus oocytes.

Main Methods:

• Utilized Xenopus oocytes, which lack endogenous RyRs, to isolate cADPR effects.
• Examined cADPR's impact on cytosolic Ca(2+) decay following Ca(2+) transients induced by inositol 1,4,5-trisphosphate (InsP(3)) and nicotinic acetylcholine receptors (nAChR).
• Employed a non-metabolizable cADPR analogue (3-Deaza-cADPR), caged cADPR, thapsigargin (SERCA inhibitor), and cADPR antagonists (8-NH(2)-cADPR, 8-br-cADPR).

Main Results:

• Intracellular injection of 3-Deaza-cADPR accelerated the decay of Ca(2+) transients in Xenopus oocytes.
• Photorelease of cADPR also rapidly enhanced Ca(2+) sequestration.
• The observed acceleration of Ca(2+) decay was abolished by SERCA inhibition with thapsigargin and blocked by cADPR antagonists.

Conclusions:

• cADPR actively enhances SERCA pump activity, thereby promoting Ca(2+) sequestration into the endoplasmic reticulum.
• This finding reveals a novel function of cADPR in regulating intracellular Ca(2+) homeostasis, complementing its known role in Ca(2+) release via RyRs.