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Peter Snyder, MD

Internal Medicine

Office: 300B EMRB
Office Phone: 319-335-5941

Lab: 371 EMRB

Lab Website: https://medicine.uiowa.edu/internalmedicine/profile/peter-snyder

Trafficking and gating of epithelial ion channels and their role in hypertension.

Our research is focused on mechanisms that regulate the ion channel ENaC and how defects cause diseases including hypertension. Much of this work is focused on channel ubiquitination and trafficking, and on the signaling pathways that regulate these processes. We discovered that a defect in ENaC endocytosis and lysosomal degradation is responsible for Liddle’s syndrome, an inherited form of hypertension. The causative mutations disrupt a binding site for Nedd4-2, an E3 ubiquitin ligase that catalyzes ENaC ubiquitination. Ubiquitination functions as a signal to induce ENaC endocytosis and targeting to lysosomes for degradation. Thus, defects in this regulation cause a pathological increase in ENaC expression at the cell surface, leading to excessive renal Na+ absorption and hypertension. We have also discovered signaling pathways that control ENaC ubiquitination. A second focus of our work is on mechanisms that control the opening and closing (gating) of ENaC. ENaC has a large highly structured extracellular domain that functions as a receptor to sense a variety of chemical and mechanical signals. These signals induce conformational changes that modulate channel gating. We are working to identify the structure-function relationships that underlie this regulation.

PubMed link

Department/Program Affiliations:
Internal Medicine
Molecular Medicine
Molecular Physiology and Biophysics