Discerning the role of mechanosensors in regulating proximal tubule function

All cells in the body experience external mechanical forces such as shear stress and stretch. These forces are sensed by specialized structures in the cell known as mechanosensors. Cells lining the proximal tubule (PT) of the kidney are continuously exposed to variations in flow rates of the glomerular ultrafiltrate, which manifest as changes in axial shear stress and radial stretch. Studies suggest that these cells respond acutely to variations in flow by modulating their ion transport and endocytic functions to maintain glomerulotubular balance. Conceptually, changes in the axial shear stress in the PT could be sensed by three known structures, namely, the microvilli, the glycocalyx, and primary cilia. The orthogonal component of the force produced by flow exhibits as radial stretch and can cause expansion of the tubule. Forces of stretch are transduced by integrins, by stretch-activated channels, and by cell-cell contacts. This review summarizes our current understanding of flow sensing in PT epithelia, discusses challenges in dissecting the role of individual flow sensors in the mechanosensitive responses, and identifies potential areas of opportunity for new study.