RRC ID 28716
Author Ehrenman K, Yang G, Hong WP, Gao T, Jang W, Brock DA, Hatton RD, Shoemaker JD, Gomer RH.
Title Disruption of aldehyde reductase increases group size in dictyostelium.
Journal J. Biol. Chem.
Abstract Developing Dictyostelium cells form structures containing approximately 20,000 cells. The size regulation mechanism involves a secreted counting factor (CF) repressing cytosolic glucose levels. Glucose or a glucose metabolite affects cell-cell adhesion and motility; these in turn affect whether a group stays together, loses cells, or even breaks up. NADPH-coupled aldehyde reductase reduces a wide variety of aldehydes to the corresponding alcohols, including converting glucose to sorbitol. The levels of this enzyme previously appeared to be regulated by CF. We find that disrupting alrA, the gene encoding aldehyde reductase, results in the loss of alrA mRNA and AlrA protein and a decrease in the ability of cell lysates to reduce both glyceraldehyde and glucose in an NADPH-coupled reaction. Counterintuitively, alrA- cells grow normally and have decreased glucose levels compared with parental cells. The alrA- cells form long unbroken streams and huge groups. Expression of AlrA in alrA- cells causes cells to form normal fruiting bodies, indicating that AlrA affects group size. alrA- cells have normal adhesion but a reduced motility, and computer simulations suggest that this could indeed result in the formation of large groups. alrA- cells secrete low levels of countin and CF50, two components of CF, and this could partially account for why alrA- cells form large groups. alrA- cells are responsive to CF and are partially responsive to recombinant countin and CF50, suggesting that disrupting alrA inhibits but does not completely block the CF signal transduction pathway. Gas chromatography/mass spectroscopy indicates that the concentrations of several metabolites are altered in alrA- cells, suggesting that the Dictyostelium aldehyde reductase affects several metabolic pathways in addition to converting glucose to sorbitol. Together, our data suggest that disrupting alrA affects CF secretion, causes many effects on cellular metabolism, and has a major effect on group size.
Volume 279(2)
Pages 837-47
Published 2004-1-9
DOI 10.1074/jbc.M310539200
PII M310539200
PMID 14551196
MeSH Aldehyde Reductase / genetics* Aldehyde Reductase / metabolism Amino Acid Sequence Animals Blotting, Northern Blotting, Western Cell Adhesion Cell Aggregation* Cell Line Cell Movement Computer Simulation Cyclic AMP / metabolism DNA / metabolism Dictyostelium / enzymology* Gas Chromatography-Mass Spectrometry Glucose / metabolism Glyceraldehyde / metabolism Molecular Sequence Data NADP / metabolism Protozoan Proteins / metabolism RNA, Messenger / metabolism Recombinant Proteins / metabolism Recombination, Genetic Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Sorbitol / metabolism Subcellular Fractions Time Factors
IF 4.106
Times Cited 14
Cellular slime molds