Pharmaceutical Sciences Seminar Series

New Players in Cardiomyocyte Calcium Signaling and Heart Function

• Jeremy T. Smyth, PhD
• Edward Hebert School of Medicine
• Uniformed Services University of the Health Sciences

Calcium is one of the most ubiquitous and diverse signaling factors in cells, and dysregulated calcium signaling is associated with numerous diseases including heart failure, neurodegeneration, and skeletal muscle myopathies. Our lab uses powerful genetic and imaging tools in the fruit fly Drosophila melanogaster to define calcium signaling functions in healthy and diseased tissues in vivo.

We recently demonstrated that the specific calcium signaling mechanism known as store-operated calcium entry (SOCE) is an essential regulator of heart function. SOCE refers to calcium influx that is activated by the depletion of endoplasmic reticulum (ER) calcium stores, and SOCE functions to replenish ER calcium stores and maintain intracellular calcium homeostasis and signaling. SOCE activation requires direct interaction between calcium sensing Stim proteins and Orai calcium influx channels specifically at ER-plasma membrane contact sites.

Importantly, our data demonstrate that both suppression and upregulation of SOCE function in cardiomyocytes results in cardiomyopathy and heart failure, suggesting that precise SOCE regulation in cardiomyocytes is essential. To this end, I will present our newest results suggesting that septin filaments are essential regulators of cardiomyocyte SOCE and heart contractility. The role of septins in the heart are completely unexplored, and our results suggest that these cytoskeletal components are new players in the regulation of heart physiology and disease pathogenesis.

Hosted by Associate Professor Arash Bashirullah.

To obtain the Webex link for this seminar, contact Debra King at Debra.King@wisc.edu.