Role Of Rab11a Positive Compartments In Endocytic Traffic In Primary Proximal Tubule Cells

The proximal tubule (PT) reabsorbs ~ 70% of sodium, bicarbonate, chloride ions, phosphate, glucose, water, and the majority of the plasma proteins from the glomerular filtrate. Despite the critical importance of endocytosis for PT cell function, the organization of the endocytic pathway in these cells remains poorly understood. We have used live‐cell imaging to dissect the itinerary of apically internalized fluid and membrane cargo in polarized primary cultures of PT cells isolated from mice. Cells from the S1 segment could be distinguished from more distal segments by their robust uptake of albumin and low expression of γ‐glutamyltranspeptidase. Rab11a in these cells is localized to numerous dynamic spherical compartments that resemble the apical vacuoles found in electron microscopy analysis of cultured PT cells. These structures are highly dynamic and receive both membrane and fluid phase cargo. In contrast, Rab11a in immortalized kidney cell lines is localized to a condensed and largely tubular apical recycling compartment through which recycling membrane proteins (but not fluid phase cargoes) transit. The unusual morphology of Rab11a‐positive compartments in primary PT cells may reflect the demands of handling a high endocytic load and suggests a possible role for Rab11a in early sorting steps of fluid and membrane proteins in these cells. This research was supported by NIH R01 DK54407 and P30 DK079307.