PTH-induced internalization of apical membrane NaPi2a: role of actin and myosin VI

Blaine J, Okamura K, Giral H, Breusegem S, Caldas Y, Millard A, Barry N, Levi M. PTH-induced internalization of apical membrane NaPi2a: role of actin and myosin VI. Am J Physiol Cell Physiol 297: C1339-C1346, 2009. First published September 23, 2009; doi:10.1152/ajpcell.00260.2009.-Parathyroid hormone (PTH) plays a critical role in the regulation of renal phosphorous homeostasis by altering the levels of the sodium-phosphate cotransporter NaPi2a in the brush border membrane (BBM) of renal proximal tubular cells. While details of the molecular events of PTH-induced internalization of NaPi2a are emerging, the precise events governing NaPi2a removal from brush border microvilli in response to PTH remain to be fully determined. Here we use a novel application of total internal reflection fluorescence microscopy to examine how PTH induces movement of NaPi2a out of brush border microvilli in living cells in real time. We show that a dynamic actin cytoskeleton is required for NaPi2a removal from the BBM in response to PTH. In addition, we demonstrate that a myosin motor that has previously been shown to be coregulated with NaPi2a, myosin VI, is necessary for PTH-induced removal of NaPi2a from BBM microvilli.