The Role of the Ion Channel TRPM7 on Intracellular Compartments

Ion channels are transmembrane proteins that regulate the conductance of a variety of ions from one side of a membrane to another, in turn generating electrical current, ionic microenvironments, and signaling cascades. While the function of most ion channels is understood in the context of the plasma membrane, a wide variety of ion channels localize to intracellular membranes where they exert unique functions to regulate organellar maintenance and signaling. One such channel is TRPM7, a ubiquitously expressed cationic channel found on both the plasma membrane and on intracellular compartments that is regulated by pH, Mg2+, and local membrane composition. In this thesis, I explore the localization and role of TPRM7 in intracellular membranes with a particular focus on viral-laden endosomes and macrophage vesicles. I define TRPM7 as a druggable target to inhibit a wide range of enveloped viral infections and provide evidence that TRPM7 functions as a counterion current to the V-ATPase in specific endosomal compartments. Lastly, I characterize the intracellular compartments in which TRPM7 resides under homeostatic conditions in various cell lines.