Membrane Biology Lab

Overview

Membrane proteins play critical roles in the brain. The Sweadner lab studies ATP-hydrolyzing enzymes that pump sodium and potassium ions against their concentration gradients, making neuronal electrophysiological activity possible.

Research Projects

We express various mutations of ATP1A3 in 293 cells and differentiated iPSC neurons to investigate how they differ. In parallel, we study their positions in crystal and cryoEM structures to determine what determines pathogenicity.

We have learned that variants that cause Alternating Hemiplegia of Childhood have a gain-of-function property that alters protein glycosylation in neurons. This is visible by microscopy and correlates with process outgrowth.

We have also determined the pathogenicity of a variant in ATP1A3 that causes onset of symptoms after childhood fevers. It proved to be labile and degraded when cells expressing it were grown at 39 degrees centigrade, in the middle of the febrile range.

Finally, we collaborate with other labs on the genetic engineering and ASO treatment of ATP1A3 disorders in mice and iPSC neurons, and in the regulation of Na,K-ATPase ATP1A1 in the choroid plexus of the brain.

Research Team

Kathleen J. Sweadner, PhD
Massachusetts General Hospital
Ksweadner@mgh.harvard.edu

Elena Arystarkhova, PhD
Massachusetts General Hospital
Earistarkhova@mgh.harvard.edu