Microtubule-assisted mechanism for functional metabolic macromolecular complex formation.
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.
An
Songon
S
Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
Deng
Yijun
Y
Tomsho
John W
JW
Kyoung
Minjoung
M
Benkovic
Stephen J
SJ
D008841:Actin Cytoskeleton / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D019733:Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D011687:Purines / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D011687:Purines; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D019733:Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; C022385:phosphoribosylformylglycinamidine synthetase; D015739:Nocodazole