Flow stimulated endocytosis in the proximal tubule

The proximal tubule plays a critical role in the reabsorption of ions, solutes and low molecular weight proteins from the glomerular filtrate. Although the proximal tubule has long been known to acutely modulate ion reabsorption in response to changes in flow rates of the glomerular filtrate, it has only recently been discovered that proximal tubule cells can similarly adjust endocytic capacity in response to flow. This review synthesizes our current understanding of mechanosensitive regulation of endocytic capacity in proximal tubule epithelia and highlights areas of opportunity for future investigations.

Recent studies have reported that the endocytic capacity of proximal tubule cells is dramatically increased upon exposure to flow and the accompanying fluid shear stress. Modulation of this pathway is dependent on increases in intracellular calcium initiated by bending of the primary cilium, and also requires purinergic receptor activation that is mediated by release of extracellular ATP. This article summarizes what is currently known about the signaling cascade that transduces changes in flow into alterations in endocytosis. We discuss the implications of this newly described regulatory pathway with respect to our understanding of protein retrieval by the kidney under normal conditions, and in diseases that present with low molecular weight proteinuria.

Primary cilia act as mechanotransducers that modulate apical endocytic capacity in proximal tubule cells in response to changes in fluid shear stress.