Role of microtubules in the rapid regulation of renal phosphate transport in response to acute alterations in dietary phosphate content.
Renal proximal tubular response to acute administration of a low Pi diet is characterized by a rapid adaptive increase in apical brush border membrane (BBM) Na-Pi cotransport activity and Na-Pi cotransporter protein abundance, independent of a change in Na-Pi cotransporter mRNA levels (Levi, M., M. Lötscher, V. Sorribas, M. Custer, M. Arar, B. Kaissling, H. Murer, and J. Biber. 1994. Am. J. Physiol. 267: F900-F908). The purposes of the present study were to determine if the acute adaptive response occurs independent of de novo protein synthesis, and if microtubules play a role in the rapid upregulation of the Na-Pi cotransporters at the apical BBM. We found that inhibition of transcription by actinomycin D and translation by cycloheximide did not prevent the rapid adaptive response. In addition, in spite of a 3.3-fold increase in apical BBM Na-Pi cotransporter protein abundance, there was no change in cortical homogenate Na-Pi cotransporter protein abundance. Pretreatment with colchicine, which resulted in almost complete disruption of the microtubular network, abolished the adaptive increases in BBM Na-Pi cotransport activity and Na-Pi cotransporter protein abundance. In contrast, colchicine had no effect on the rapid downregulation of Na-Pi cotransport in response to acute administration of a high Pi diet. We conclude that the rapid adaptive increase in renal proximal tubular apical BBM Na-Pi cotransport activity and Na-Pi cotransporter abundance is independent of de novo protein synthesis, and is mediated by microtubule-dependent translocation of presynthesized Na-Pi cotransporter protein to the apical BBM.
Lötscher
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75216, USA.
Kaissling
B
B
Biber
J
J
Murer
H
H
Levi
M
M
D000222:Adaptation, Physiological; D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002451:Cell Compartmentation; D004032:Diet; D015536:Down-Regulation; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008870:Microtubules / Q000502:physiology*; D010710:Phosphates / Q000008:administration & dosage / Q000378:metabolism* / Q000502:physiology; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D010710:Phosphates; D012964:Sodium