Partitioning of the plasma membrane Ca2+-ATPase into lipid rafts in primary neurons: effects of cholesterol depletion
Article first published online: 5 FEB 2007
Journal of Neurochemistry
Volume 102, Issue 2, pages 378–388, July 2007
How to Cite
Jiang, L., Fernandes, D., Mehta, N., Bean, J. L., Michaelis, M. L. and Zaidi, A. (2007), Partitioning of the plasma membrane Ca2+-ATPase into lipid rafts in primary neurons: effects of cholesterol depletion. Journal of Neurochemistry, 102: 378–388. doi: 10.1111/j.1471-4159.2007.04480.x
- Issue published online: 5 FEB 2007
- Article first published online: 5 FEB 2007
- Received November 3, 2006; revised manuscript received January 5, 2007; accepted January 19, 2007.
- lipid rafts;
- plasma membrane Ca2+-ATPase
Spatial and temporal alterations in intracellular calcium [Ca2+]i play a pivotal role in a wide array of neuronal functions. Disruption in Ca2+ homeostasis has been implicated in the decline in neuronal function in brain aging and in neurodegenerative disorders. The plasma membrane Ca2+-ATPase (PMCA) is a high affinity Ca2+ transporter that plays a crucial role in the termination of [Ca2+]i signals and in the maintenance of low [Ca2+]i essential for signaling. Recent evidence indicates that PMCA is uniquely sensitive to its lipid environment and is stimulated by lipids with ordered acyl chains. Here we show that both PMCA and its activator calmodulin (CaM) are partitioned into liquid-ordered, cholesterol-rich plasma membrane microdomains or ‘lipid rafts’ in primary cultured neurons. Association of PMCA with rafts was demonstrated in preparations isolated by sucrose density gradient centrifugation and in intact neurons by confocal microscopy. Total raft-associated PMCA activity was much higher than the PMCA activity excluded from these microdomains. Depletion of cellular cholesterol dramatically inhibited the activity of the raft-associated PMCA with no effect on the activity of the non-raft pool. We propose that association of PMCA with rafts represents a novel mechanism for its regulation and, consequently, of Ca2+ signaling in the central nervous system.