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

• Published in: American Journal of Physiology: Cell Physiology 2009-12, Vol.297 (6), p.C1339-C1346
• Main Authors: Blaine, Judith, Okamura, Kayo, Giral, Hector, Breusegem, Sophia, Caldas, Yupanqui, Millard, Andrew, Barry, Nicholas, Levi, Moshe
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells; Cells, Cultured; Cytoskeleton - metabolism; Genes, Dominant; Hormones; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - metabolism; Kidneys; Membrane Transporters, Ion Channels, and Pumps; Membranes; Microscopy; Microscopy, Confocal; Microscopy, Fluorescence - methods; Microvilli - drug effects; Microvilli - metabolism; Myosin Heavy Chains - metabolism; Opossums; Parathyroid Hormone - pharmacology; Phosphorus; Sodium; Sodium-Phosphate Cotransporter Proteins, Type IIa - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00260.2009

Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado Submitted 17 June 2009 ; accepted in final form 15 September 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. apical total internal reflection fluorescence microscopy; parathyroid hormone Address for reprint requests and other correspondence: J. Blaine, Univ. of Colorado at Denver, Division of Renal Diseases and Hypertension, 12700 E 19th Ave., Campus Box C281, Aurora, CO 80045 (e-mail: Judith.Blaine{at}ucdenver.edu ).