Hypothesis: control of intracellular calcium level.

Area of Science:

• Cell Biology
• Biochemistry
• Membrane Biophysics

Background:

• Cellular calcium (Ca2+) homeostasis is crucial for numerous physiological processes.
• Acidic phospholipids, such as phosphatidylinositol and phosphatidylserine, are abundant in cell membranes.

Purpose of the Study:

• To propose a novel mechanism for cellular calcium storage and release.
• To elucidate the role of acidic phospholipids in forming calcium-binding cages.
• To investigate the inositide shuttle as a regulator of cytoplasmic Ca2+.

Main Methods:

• Analysis of the [Ca(phosphatidate)2] complex properties.
• Thermodynamic considerations of calcium cage stability and dissociation.
• Hypothesizing the role of phospholipid phosphorylation in calcium release.

Main Results:

• Calcium ions (Ca2+) are proposed to be stored in cages formed by acidic phospholipids on the cytoplasmic side of membranes.
• The dissociation constant for these calcium cages aligns with physiological cytoplasmic Ca2+ concentrations (~10^-7 M).
• Phosphorylation of inositol headgroups disrupts cage stability, facilitating Ca2+ release into the cytosol.

Conclusions:

• The inositide shuttle (mono-, di-, triphosphoinositides) acts as a regulator of cytoplasmic Ca2+ concentration.
• Phosphorylation of inositides increases cytoplasmic Ca2+, while dephosphorylation decreases it.
• This mechanism may link to stimulus-induced inositol triphosphate generation and calcium transport across membranes.