Microtubule-assisted mechanism for functional metabolic macromolecular complex formation

Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):12872-6. doi: 10.1073/pnas.1008451107. Epub 2010 Jul 6.

Abstract

Evidence has been presented for a metabolic multienzyme complex, the purinosome, that participates in de novo purine biosynthesis to form clusters in the cytoplasm of living cells under purine-depleted conditions. Here we identified, using fluorescent live cell imaging, that a microtubule network appears to physically control the spatial distribution of purinosomes in the cytoplasm. Application of a cell-based assay measuring the rate of de novo purine biosynthesis confirmed that the metabolic activity of purinosomes was significantly suppressed in the absence of microtubules. Collectively, we propose a microtubule-assisted mechanism for functional purinosome formation in HeLa cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Biological Transport / drug effects
  • Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor / metabolism
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Macromolecular Substances / metabolism*
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Multienzyme Complexes / metabolism
  • Nocodazole / pharmacology
  • Purines / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism

Substances

  • Macromolecular Substances
  • Multienzyme Complexes
  • Purines
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
  • phosphoribosylformylglycinamidine synthetase
  • Nocodazole