title: Effects of gangliosides on the activity of the plasma membrane Ca2+-ATPase.
abstract: Control of intracellular calcium concentrations ([Ca(2+)]i) is essential for neuronal function, and the plasma membrane Ca(2+)-ATPase (PMCA) is crucial for the maintenance of low [Ca(2+)]i. We previously reported on loss of PMCA activity in brain synaptic membranes during aging. Gangliosides are known to modulate Ca(2+) homeostasis and signal transduction in neurons. In the present study, we observed age-related changes in the ganglioside composition of synaptic plasma membranes. This led us to hypothesize that alterations in ganglioside species might contribute to the age-associated loss of PMCA activity. To probe the relationship between changes in endogenous ganglioside content or composition and PMCA activity in membranes of cortical neurons, we induced depletion of gangliosides by treating neurons with d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP). This caused a marked decrease in the activity of PMCA, which suggested a direct correlation between ganglioside content and PMCA activity. Neurons treated with neuraminidase exhibited an increase in GM1 content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity that was greater than that produced by d-PDMP treatment. Thus, it appeared that poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides had the opposite effect. Our observations add support to previous reports of PMCA regulation by gangliosides by demonstrating that manipulations of endogenous ganglioside content and species affect the activity of PMCA in neuronal membranes. Furthermore, our studies suggest that age-associated loss in PMCA activity may result in part from changes in the lipid environment of this Ca(2+) transporter.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA. Electronic address: jianglei@ku.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Misty D
authors.initials: MD
authors.lastname: Bechtel
authors.affiliation: Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA; Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bean
authors.affiliation: Structural Biology Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Winefield
authors.affiliation: Structural Biology Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Todd D
authors.initials: TD
authors.lastname: Williams
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA; Department of Biochemistry, Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Zaidi
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Elias K
authors.initials: EK
authors.lastname: Michaelis
authors.affiliation: Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA; Higuchi Biosciences Center, University of Kansas, Lawrence, KS, USA.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Michaelis
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D005732:Gangliosides / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D051381:Rats
chemical_list: D005732:Gangliosides; D000252:Calcium-Transporting ATPases; D002118:Calcium
keywords: Aging; Calcium; Ganglioside; Neuraminidase; Plasma membrane Ca(2+)-ATPase; d(l)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP)