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Plasma membrane calcium ATPases as critical regulators of calcium homeostasis during neuronal cell function
1Ludwig Institute for Cancer Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA.
Abstract:
The plasma membrane calcium ATPases (PMCAs) are ubiquitously expressed proteins that couple the extrusion of calcium across the plasma membrane with the hydrolysis of ATP. In mammals, four separate genes encode distinct PMCA isoforms. Complex patterns of alternative RNA splicing generate additional isoform variability. Functionally, the PMCAs were originally assigned the role of maintaining basal levels of intracellular calcium. Recent evidence, however, is expanding the role of the PMCAs as important participants in dynamic Ca2+ regulation and as crucial players of Ca2+ export during normal and pathological conditions. This review highlights recent advances made on the biology of the PMCAs within the context of neuronal development, cellular responses to external stimuli and cell survival. Particular emphasis is placed on the role of the PMCAs in vestibular and auditory functions, localized calcium signaling in photoreceptor synaptic terminals and calcium-mediated cell death.
Insights
Plasma membrane calcium ATPases (PMCAs) are vital for calcium regulation. Emerging research reveals their expanded roles in neuronal development, cellular responses, and survival, impacting hearing, vision, and cell death.
Area of Science:
- Molecular Biology
- Cell Physiology
- Neuroscience
Background:
- Plasma membrane calcium ATPases (PMCAs) are essential for extruding calcium ions (Ca2+) from cells.
- Four mammalian genes encode distinct PMCA isoforms, with alternative splicing adding further complexity.
- Initially recognized for maintaining basal intracellular calcium, PMCAs are now understood to play dynamic regulatory roles.
Purpose of the Study:
- To review recent advancements in the biology of PMCAs.
- To highlight the involvement of PMCAs in neuronal development, cellular responses, and cell survival.
- To emphasize the specific roles of PMCAs in auditory and vestibular functions, photoreceptor signaling, and calcium-mediated cell death.
Main Methods:
- Literature review of recent research on PMCA function and biology.
- Synthesis of findings related to PMCA roles in various physiological and pathological contexts.
- Focus on specific examples including sensory functions and cell death pathways.
Main Results:
- Evidence supports expanded roles for PMCAs beyond basal calcium maintenance.
- PMCAs are crucial in dynamic Ca2+ signaling and export during normal and disease states.
- Specific PMCA functions are implicated in neuronal development, sensory processing, and cell fate.
Conclusions:
- PMCAs are critical regulators of cellular calcium homeostasis with diverse functions.
- Recent studies underscore the significance of PMCAs in complex physiological processes.
- Further investigation into PMCA roles is warranted for understanding health and disease.