Nuclear localizations of phosphatidylinositol 5-phosphate 4-kinases α and β are dynamic and independently regulated during starvation-induced stress.

Research output: Contribution to journalArticlepeer-review

  • Authors:
  • Alaa Droubi
  • Simon J. Bulley
  • J H Clarke
  • R. F. Irvine

Abstract

The chicken B-cell line DT40 has two isoforms of phosphatidylinositol 5-phosphate 4-kinase (PI5P4K), α and β, likely to exist as a mix of obligate homo- and hetero-dimers. Previous work has led us to speculate that an important role of the b isoform may be to target the more active PI5P4Kα isoform to the nucleus. Here we expand upon that work by genomically tagging the PI5P4Ks with fluorochromes in the presence or absence of stable or acute depletions of PI5P4Kb. Consistent with our original hypothesis we find that PI5P4Kα is predominantly (possible entirely) cytoplasmic when PI5P4Kb is stably deleted from cells. In contrast, when PI5P4Kb is inducibly removed within an hour PI5P4Kα retains its wild type distribution of approximately 50:50 between cytoplasm and nucleus even through a number of cell divisions. This leads us to speculate that PI5P4Kα is chromatin associated. We also find that when cells are in the exponential phase of growth PI5P4Kb is primarily cytoplasmic but translocates to the nucleus upon growth into the stationary phase or upon serum starvation. Once again this is not accompanied by a change in PI5P4Kα localization and we show, using an <em>in vitro</em> model, that this is possible because the dimerization between the two isoforms is dynamic. Given this shift in PI5P4Kb upon nutrient deprivation we explore the phenotype of PI5P4Kb null cells exposed to this stress and find that they can sustain a greater degree of nutrient deprivation than their wild type counterparts possibly as a result of upregulation of autophagy.

Bibliographical metadata

Original languageEnglish
Pages (from-to)2155-2163
JournalThe Biochemical Journal
Volume473
Issue number14
Early online date16 May 2016
DOIs
Publication statusPublished - 2016