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J. Biol. Chem., Vol. 279, Issue 2, 837-847, January 9, 2004

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Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium^*

Karen Ehrenman, Gong Yang, Wan-Pyo Hong, Tong Gao, Wonhee Jang, Debra A. Brock, R. Diane Hatton, James D. Shoemaker¶, and Richard H. Gomer||

From the Howard Hughes Medical Institute and Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005-1892 and the ^¶Metabolic Screening Laboratory, Department of Biochemistry and Molecular Biology, St. Louis University, St. Louis, Missouri 63104

Developing Dictyostelium cells form structures containing 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.

Received for publication, September 23, 2003

^* The D. discoideum sequencing consortium was funded by the Deutsche Forschungsgemeinschaft, the National Institutes of Health, the Medical Research Council, and the European Union. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| An Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Howard Hughes Medical Institute and Dept. of Biochemistry and Cell Biology, MS-140, Rice University, 6100 S. Main St., Houston, TX 77005-1892. Tel.: 713-348-4872; Fax: 713-348-5154; E-mail: richard{at}bioc.rice.edu.

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