PTH-induced internalization of apical membrane NaPi2a: role of actin and myosin VI.
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.
Department of Medicine, University of Colorado Denver, Aurora, 80045, USA. Judith.Blaine@ucdenver.edu
Judith
J
Blaine
Kayo
K
Okamura
Hector
H
Giral
Sophia
S
Breusegem
Yupanqui
Y
Caldas
Andrew
A
Millard
Nicholas
N
Barry
Moshe
M
Levi
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005799:Genes, Dominant; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism*
D000199:Actins; D010281:Parathyroid Hormone; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; C089785:myosin VI; D018995:Myosin Heavy Chains