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It is well recognized that an increase in glomerular filtration rate leads to an increase in fluid, Na+ and HCO3− absorption in proximal tubules; however, underlying mechanisms of this modulation have not been delineated. This review provides an update of flow-activated transport events along the nephron. Transporters, flow-sensors and secondary messengers that may modulate flow are also discussed.We have demonstrated that both NHE3 and H-ATPase activities are modulated by axial flow in mouse proximal tubules in vitro. Experimental data and modeling calculations provide strong evidence that brush-border microvilli function as flow sensors in the proximal tubule. In addition, AngII receptor localization is regulated by flow in cultured proximal tubule cells, and flow induces eNOS translocation in TAL.Flow-modulated NHE3 activity is the regulatory mechanism for GTB. It is independent of neuron and systemic hormonal regulation, but requires the intact actin cytoskeleton to transmit the signal of altered axial flow sensed by brush-border microvilli. Unanswered questions include the identification of specific signaling transduction mechanisms and second messengers in response to flow. Whether the Na+/2Cl–/K+-cotransporter in TAL is flow-activated, and whether a divalent cation, Ca2+ and Mg2+ transport, can be regulated by flow is unknown.