Frost lab preprint from Claira Sohn! Elevation of the mechanically-sensitive protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons

Cells detect and respond to mechanical forces that shape their function and survival through a process termed “mechanotransduction.” While well studied outside of the brain, little is known regarding neuronal mechanotransduction despite exposure of the brain to vascular flow, movement, injury, and disease.

This study was an outgrowth of our original finding that tau destabilizes the nucleoskeleton in neurons and drives nuclear envelope blebbing and invagination (2016 Frost et al. Current Biology). Claira subsequently discovered that nuclear tension is reduced in a cellular model of tauopathy (2023 Sohn et al. Frontiers in Aging).

Led by proteomics, we now hone in on a specific protein, emerin, that is elevated in cell culture models of tauopathy. Emerin is a central regulator of nuclear mechanotransduction that allows cells to sense and respond to cellular force. Claira finds that emerin overexpression in cultured neurons is sufficient to drive toxicity, increase filamentous actin, and induce nuclear invagination, cellular phenotypes that also occur in settings of tauopathy. She further finds that emerin relocalizes from the nucleus to the cytosol in a cellular model of tauopathy, where it has increased interaction with cytoskeletal regulators.

Our findings lay the groundwork for future studies on the role of emerin and altered nuclear mechanotransduction in neurodegenerative tauopathies and highlight an emerging function of emerin as a regulator of nuclear mechanotransduction in neurons.

Thank you to coauthors Sammy Pardo, Dana Molleur, Satvik Paduri, Morgan Lambert, Morgan Thomas, Erich Sohn, and Susan Weintraub. This study was supported by an a National Institute of Neurological Disorders and Stroke (NINDS) F31 awarded to Claira and an R01 from the National Institute on Aging (NIA).

Check out the preprint!