Changing PIP2 Over Time

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane lipid that serves as a substrate for the production of signaling messengers, as well as a direct regulator of the activity of proteins in various cellular compartments through its presence in cellular membranes. Heilmann et al. analyzed the amounts of PIP2 and the amount and activity of phosphatidylinositol phosphate kinase (PIPK) in the plasma membrane and microsomal membrane preparations of the thermo-acidophilic red algae Galdieria sulphuraria. Their results show that during stationary growth in culture, the plasma membrane amounts of PIP2 and the activity and amount of PIPK decrease. In microsomal membranes, the amount of PIP2 and the activity of PIPK increase during the same time period. In cells exposed to mild hyperosmotic conditions, the amounts of inositol trisphosphate (IP3) produced were the same in 7-day or 12-day cultures. However, the 12-day cultures showed increased activity of PIPK, suggesting that increased synthesis of PIP2 was required to maintain the plasma membrane pool in the older cells. To assess whether the decreased plasma membrane pool of PIP2 could impact signaling, the response of cells exposed to mild or extreme osmotic shock were compared in terms of PIP2 production. Older cells were unable to respond to the more extreme stress with the comparable production of IP3 despite strong activation of PIPK, suggesting that the PIP2 pool had been depleted sufficiently to decrease signaling output. The results presented here imply two findings important for signal transduction: (i) the intracellular and plasma membrane pools of PIP2 are regulated separately, and (ii) changes in plasma membrane concentrations of PIP2 can alter the amplitude of signals dependent on metabolism of this precursor. The question remains open regarding whether the changes in the PIP2 in the cellular membranes have any direct consequences for altering protein activity in these separate cellular domains.I. Heilmann, I. Y. Perera, W. Gross, W. F. Boss, Plasma membrane phosphatidylinositol 4,5-bisphosphate levels decrease with time in culture. Plant Physiol. 126, 1507-1518 (2001). [Abstract][Full Text]