Sci. Signal., 17 February 2009
Cell Biology The Lure of Lipids
Annalisa M. VanHook
Science Signaling, AAAS, Washington, DC 20005, USA
In the Drosophila melanogaster embryo, germ cell migration from the posterior pole to the mesodermally derived gonad requires the activities of type I geranylgeranyl transferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), an enzyme of the isoprenoid biosynthetic pathway. Misexpression of hmgcr is sufficient to attract germ cells to ectopic sites, suggesting that some central component of the guidance system, perhaps the germ cell attractant itself, requires geranylation. Because lipid-modified proteins are secreted through adenosine triphosphate–binding cassette (ABC) transporters in yeast, Ricardo and Lehmann tested whether components of an analogous transport system were required for germ cell migration in Drosophila. multidrug resistance 49 (mdr49), which encodes a functional homolog of the yeast ABC transporter STE6, was expressed in the mesoderm and required in that tissue for proper germ cell migration. STE6, which mediates the secretion of farnesylated yeast mating pheromone, could substitute for Mdr49 and direct germ cell migration to the mesoderm. Enzymes required for processing prenylated proteins were also necessary for germ cell migration, thus implicating a secreted lipid-modified peptide in the chemoattraction of germ cells to the gonad. Both Mdr49 and HMGCR were required for cultured cells to secrete a germ cell–attracting factor into the culture medium, but components of the signal peptide–dependent secretion pathway were not. Thus, the ABC transporter system, generally associated with pumping toxins out of cells, may also be employed to export signaling molecules in animals (see the Perspective by Hla and Im).
Citation: A. M. VanHook, The Lure of Lipids. Sci. Signal. 2, ec59 (2009).
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