MS Defense - Ryan B. Williams

August 12, 2021

2:00 pm


Calmodulinopathy: Is Calcineurin the Missing Link?

Ryan B. Williams

Department of Chemistry
Mississippi State University

Thursday, August 12, 2021
1:00 PM
Hand Lab 2231


Abstract

     Calmodulin (CaM) is a ubiquitous calcium sensing protein that regulates numerous proteins throughout the body. In response to changes in Ca2+ concentration CaM modifies, activates, and de-activates enzymes and ion channels, as well as many other cellular processes. The importance of CaM is highlighted by the conservation of an identical amino acid sequence in all mammals. Alterations in CaM were once thought to be incompatible with life. Within the last decade mutations in CaM have been identified in patients suffering from life-threatening heart diseases (Long QT and CPVT). Thus far inadequate or untimely interaction between mutant CaM and several proteins (LTCC, RyR2, and CaMKII) have been identified as mechanisms underlying calmodulinopathy. Given the extensive number of CaM interactions in the body, there are likely many consequences for altering CaM sequence. Here, we demonstrate that several of the disease associated CaM mutations alter the sensitivity and activity of the Ca2+-CaM enhanced serine/threonine phosphatase calcineurin (CaN). We find that the individual CaM mutations modify CaN functionality by different mechanisms. These results suggest that CaN dysfunction may contribute to Calmodulinopathy.


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