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

Am J Physiol Cell Physiol. 2009 Dec;297(6):C1339-46. doi: 10.1152/ajpcell.00260.2009. Epub 2009 Sep 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytoskeleton / metabolism
  • Genes, Dominant
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism*
  • Microscopy, Confocal
  • Microscopy, Fluorescence / methods
  • Microvilli / drug effects
  • Microvilli / metabolism
  • Myosin Heavy Chains / metabolism*
  • Opossums
  • Parathyroid Hormone / pharmacology*
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism*

Substances

  • Actins
  • Parathyroid Hormone
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • myosin VI
  • Myosin Heavy Chains