Cdc42 activation couples fluid shear stress to apical endocytosis in proximal tubule cells.

Cells lining the kidney proximal tubule (PT) respond to acute changes in glomerular filtration rate and the accompanying fluid shear stress (FSS) to regulate reabsorption of ions, glucose, and other filtered molecules and maintain glomerulotubular balance. Recently, we discovered that exposure of PT cells to FSS also stimulates an increase in apical endocytic capacity (Raghavan et al. PNAS, 111:8506-8511, 2014).

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.

Flow stimulated endocytosis in the proximal tubule.

Purpose Of Review: 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.

Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia.

The kidney has an extraordinary ability to maintain stable fractional solute and fluid reabsorption over a wide range of glomerular filtration rates (GFRs). Internalization of filtered low molecular weight proteins, vitamins, hormones, and other small molecules is mediated by the proximal tubule (PT) multiligand receptors megalin and cubilin. Changes in GFR and the accompanying fluid shear stress (FSS) modulate acute changes in PT ion transport thought to be mediated by microvillar bending.

Rab11a-positive compartments in proximal tubule cells sort fluid-phase and membrane cargo.

The proximal tubule (PT) reabsorbs the majority of sodium, bicarbonate, and chloride ions, phosphate, glucose, water, and plasma proteins from the glomerular filtrate. Despite the critical importance of endocytosis for PT cell (PTC) function, the organization of the endocytic pathway in these cells remains poorly understood. We have used immunofluorescence and live-cell imaging to dissect the itinerary of apically internalized fluid and membrane cargo in polarized primary cultures of PTCs isolated from mouse kidney cortex.

MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons.

MicroRNA (miRNA) functions in the pathogenesis of major neurodegenerative diseases such as Alzheimer's disease (AD) are only beginning to emerge. We have observed significantly elevated levels of a specific miRNA, miR-26b, in the defined pathological areas of human postmortem brains, starting from early stages of AD (Braak III). Ectopic overexpression of miR-26b in rat primary postmitotic neurons led to the DNA replication and aberrant cell cycle entry (CCE) and, in parallel, increased tau-phosphorylation, which culminated in the apoptotic cell death of neurons.