ENaC Proteins as Mechanosensors in Endothelial and Vascular Smooth Muscle Cells

Symposium — Sunday, April 22, 2018 — 1:30 PM - 3:00 PM — Convention Center, Room 25A
Renal Section — Chair: Heather Drummond — Co-Chair: Zoe Ashley

Mechanosensing is an evolutionarily conserved process that is inherent to nearly all cell mammalian types.  It underlies our ability for hearing, coordinated movement, bone growth/reabsorption and muscle contraction, among many other processes.  Within the vascular system, endothelial and smooth muscle cells acutely sense shear stress and stretch, respectively, to regulate local blood flow and pressure in certain organs, including the kidney.  Since the loss of flow and pressure regulation in the renal microvasculature is linked to end-organ injury, understanding the mechanisms underlying force sensing in the renal vasculature is critical to the prevention of end-organ injury.   In the model systems of the drosophila and nematode, a large body of behavioral, biochemical, and electrophysiological evidence points to a specific family of proteins as mechano-electrical couplers.  This protein family, termed degenerins, includes the mammalian Epithelial Na⁺ Channel (ENaC) and Acid Sensing Ion Channel (ASIC) proteins.  Yet, the importance of ENaC/ASIC proteins in initiation of force sensing in vascular tissue remains largely unrecognized among the vascular biology community in favor of extracellular matrix-integrin interactions, cytoskeletal proteins, membrane bound enzyme and second messenger systems, receptors, ion transporters/exchanger mechanisms. This symposium will include speakers from the three leading laboratories investigating ENaC/ASIC channels in vascular mechanosensing.  The symposium is designed to provide a discussion of evolutionary evidence supporting a role for ENaC/ASIC in mechanoelectrical coupling and current state of the art understanding of the role and importance of ENaC/ASIC proteins in sensing shear force and stretch in vascular tissues and the consequences of altered ENaC function.  Additionally, it will discuss a role for second messenger systems, Trp and integrins in post mechano-electrical coupling signaling (i.e. signal amplification).  Thomas Kleyman, M.D., Professor of Medicine, University of Pittsburgh, an expert in the structure-function of ENaC, will provide an overview of the evolutionary evidence in support of the ENaC/ASIC family as mechanosensors.  Heather Drummond, Ph.D., Professor of Physiology, University of Mississippi Medical Center, will discuss evidence supporting ENaC/ASIC as a mechano-electrical coupler in vascular smooth muscle cells and how ENaC maybe coupled to Trp channels to amplify the signal.  Dr. Shujie Shi, an Instructor in Dr. Kleyman’s laboratory, will discuss structural elements in ENaC required for mechanosensing in vascular tissues.  Finally, Martin Fronius, Ph.D., Senior Lecturer, Department of Physiology, University of Otago, New Zealand, will discuss the role of the extracellular matrix in shear force sensing of ENaC in endothelial cells.  The presentations will also discuss how ENaC signaling is integrated into some of the known down-stream signaling pathways important in vascular mechanosensing.

Speakers

• ENaC: An evolutionary model of mechano-electrical coupling.
  Thomas Kleyman — Medicine, Universit of Pittsburgh


• Mechanotransduction in renal VSMCs is mediated by coupling of ENaC and Trp signaling.
  Heather Drummond — Physiology and Biophysics, University of Mississippi Medical Center


• How do ENaCs sense mechanical force? Or extracellular Na+ regulates ENaC function in blood vessels.
  Shujie Shi — Medicine, University of Pittsburgh


• Shear force sensing of ENaC in endothelial cells requires N-glycans and the extracellular matrix.
  Martin Fronius — Physiology, University of Otago,


• COCHAIR
  Zoe Ashley —