Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster.
The discovery of large supramolecular complexes such as the purinosome suggests that subcellular organization is central to enzyme regulation. A screen of the yeast GFP strain collection to identify proteins that assemble into visible structures identified four novel filament systems comprised of glutamate synthase, guanosine diphosphate-mannose pyrophosphorylase, cytidine triphosphate (CTP) synthase, or subunits of the eIF2/2B translation factor complex. Recruitment of CTP synthase to filaments and foci can be modulated by mutations and regulatory ligands that alter enzyme activity, arguing that the assembly of these structures is related to control of CTP synthase activity. CTP synthase filaments are evolutionarily conserved and are restricted to axons in neurons. This spatial regulation suggests that these filaments have additional functions separate from the regulation of enzyme activity. The identification of four novel filaments greatly expands the number of known intracellular filament networks and has broad implications for our understanding of how cells organize biochemical activities in the cytoplasm.
Noree
Chalongrat
C
Section of Cell and Developmental Biology, University of California-San Diego, La Jolla, CA 92093, USA.
Sato
Brian K
BK
Broyer
Risa M
RM
Wilhelm
James E
JE
D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D020717:Eukaryotic Initiation Factor-2B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009713:Nucleotidyltransferases; D011328:Prions / Q000096:biosynthesis; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000378:metabolism
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D020717:Eukaryotic Initiation Factor-2B; D011328:Prions; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D009713:Nucleotidyltransferases; C026917:mannose 1-phosphate guanylyltransferase; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D019311:Staurosporine