Loading...
Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats
Jiang, Lei Bechtel, Misty D. Galeva, Nadezhda A. Williams, Todd D. Michaelis, Elias K. Michaelis, Mary Lou
Jiang, Lei
Bechtel, Misty D.
Galeva, Nadezhda A.
Williams, Todd D.
Michaelis, Elias K.
Michaelis, Mary Lou
Citations
Altmetric:
Abstract
Precise regulation of free intracellular Ca2+ concentrations [Ca2+]i is critical for normal neuronal function, and alterations in Ca2+ homeostasis are associated with brain aging and neurodegenerative diseases. One of the most important proteins controlling [Ca2+]i is the plasma membrane Ca2+-ATPase (PMCA), the high affinity transporter that fine tunes the cytosolic
nanomolar levels of Ca2+. We previously found that PMCA protein in synaptic plasma membranes (SPMs) is decreased with advancing age and the decrease in enzyme activity is much greater than that in protein levels. In the present study, we isolated raft and non-raft fractions from rat brain SPMs and used quantitative mass spectrometry to show that the specialized lipid microdomains in SPMs, the rafts, contain 60% of total PMCA, comprised of all four isoforms. The raft PMCA pool had the highest specific activity and this decreased progressively with age. The reduction in PMCA protein could not account for the dramatic activity loss. Addition of excess CaM to the assay did not restore PMCA activity to that in young brains. Analysis of the major raft lipids revealed a slight age-related increase in cholesterol levels and such increases might enhance membrane lipid order and prevent further loss of PMCA activity.
Description
Date
2012-12
Journal Title
Journal ISSN
Volume Title
Publisher
Wiley
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
PMCA, Brain aging, Calcium, Synaptic rafts, Protein mass spectrometry, Calmodulin
Citation
Jiang, L., Bechtel, M. D., Galeva, N. A., Williams, T. D., Michaelis, E. K., & Michaelis, M. L. (2012). Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats. Journal of Neurochemistry, 123(5), 689–699. http://doi.org/10.1111/j.1471-4159.2012.07918.x