Ca2+ transport by sarco/endoplasmic reticulum, tightly coupled with the enzymatic activity of Ca2+ -dependent
ATPase, controls the cell cycle through the regulation of genes operating in the critical G, to S checkpoint. Experimental studies demonstrated that
acylphosphatase actively hydrolyses the phosphorylated intermediate of sarco/endoplasmic reticulum
calcium ATPase (SERCA) and therefore enhances the activity of Ca2+ pump. In this study we found that SH-SY5Y
neuroblastoma cell division was blocked by entry into a quiescent G0-like state by
thapsigargin, a high specific SERCA inhibitor, highlighting the regulatory role of SERCA in cell cycle progression. Addition of physiological amounts of
acylphosphatase to SY5Y membranes resulted in a significant increase in the rate of
ATP hydrolysis of SERCA. In synchronized cells a concomitant variation of the level of
acylphosphatase isoenzymes opposite to that of intracellular free
calcium during the G1 and S phases occurs. Particularly, during G1 phase progression the
isoenzymes content declined steadily and hit the lowest level after 6 h from G0 to G1 transition with a concomitant significant increase of
calcium levels. No changes in free
calcium and
acylphosphatase levels upon
thapsigargin inhibition were observed. Moreover, a specific binding between
acylphosphatase and SERCA was demonstrated. No significant change in SERCA-2 expression was found. These findings suggest that the hydrolytic activity of
acylphosphatase increase the turnover of the phosphoenzyme intermediate with the consequences of an enhanced efficiency of
calcium transport across endoplasmic reticulum and a subsequent decrease in cytoplasmic
calcium levels. A hypothesis about the modulation of SERCA activity by
acylphosphatase during cell cycle in SY5Y cells in discussed.