Calcium Signaling in Microglia
Session Number
Project ID: BIO 09
Advisor(s)
Murali Prakriya; Northwestern University, Department of Pharmacology, Feinberg School of Medicine
Megumi Yamashita; Northwestern University, Department of Pharmacology, Feinberg School of Medicine
Timothy Kountz; Northwestern University, Department of Pharmacology, Feinberg School of Medicine
Discipline
Biology
Start Date
22-4-2020 9:10 AM
End Date
22-4-2020 9:25 AM
Abstract
Microglia are macrophage cells found throughout the brain and spinal cord, and they function as the main form of active immune defense in the central nervous system. In a normal, healthy brain, resting state microglia have a ramified morphology. After a pathological event, however, microglia transform into an activated form that has amoeboid morphology, by sensing factors that trigger cellular remodeling into the active state. Receptor-induced Ca2+ signals play a central role in microglial activation and function. Calcium signals are maintained by a process involving store-operated calcium entry (SOCE), namely the opening of plasma membrane Ca2+ channels after the release of Ca2+ from intracellular stores. Once depletion has occurred, stromal interaction molecules (STIM) sense the reduced level of Ca2+ and in response, activates the channel protein Orai and promotes Ca2+ refilling. SOCE dysregulation may trigger a disruption of intracellular Ca2+ signaling in glial cells, resulting in the pathogenesis of neurodegenerative diseases. In many immune cells, SOCE plays a central role to calcium signaling, however, it is not yet known whether this is the case with microglia. We hope to understand the properties of SOCE for microglia activation, and how extrinsic factors such as the bacterial lipopolysaccharide (LPS) protein, which activates microglia, affects SOCE. These studies will help illustrate basic calcium signaling in microglia as well as how the pathway is activated by microglia activation.
Calcium Signaling in Microglia
Microglia are macrophage cells found throughout the brain and spinal cord, and they function as the main form of active immune defense in the central nervous system. In a normal, healthy brain, resting state microglia have a ramified morphology. After a pathological event, however, microglia transform into an activated form that has amoeboid morphology, by sensing factors that trigger cellular remodeling into the active state. Receptor-induced Ca2+ signals play a central role in microglial activation and function. Calcium signals are maintained by a process involving store-operated calcium entry (SOCE), namely the opening of plasma membrane Ca2+ channels after the release of Ca2+ from intracellular stores. Once depletion has occurred, stromal interaction molecules (STIM) sense the reduced level of Ca2+ and in response, activates the channel protein Orai and promotes Ca2+ refilling. SOCE dysregulation may trigger a disruption of intracellular Ca2+ signaling in glial cells, resulting in the pathogenesis of neurodegenerative diseases. In many immune cells, SOCE plays a central role to calcium signaling, however, it is not yet known whether this is the case with microglia. We hope to understand the properties of SOCE for microglia activation, and how extrinsic factors such as the bacterial lipopolysaccharide (LPS) protein, which activates microglia, affects SOCE. These studies will help illustrate basic calcium signaling in microglia as well as how the pathway is activated by microglia activation.