MICROBIOLOGY/DEVELOPMENT

Cutting Both Ways

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Science  27 Sep 2002:
Vol. 297, Issue 5590, pp. 2173
DOI: 10.1126/science.297.5590.2173a

Cells need to be able to communicate with other cells, either within a multicellular organism (during development) or in a population of bacteria (during quorum sensing), and this need is manifest in the enormous variety of mechanisms for generating and receiving signals. One recently discovered pathway for producing signaling molecules (peptides) from inactive membrane-embedded precursors involves, in Drosophila, the cleavage of the ligand precursor Spitz by the serine protease Rhomboid. Two noteworthy aspects of this reaction are that the protease cuts the precursor at an intramembrane site and that it takes place in an internal compartment, after which the now-soluble ligand is secreted.

The human pathogen Providencia stuartii contains a Rhomboid-like protein, AarA, that is known to be involved in sensing its population density. Gallio et al. show that AarA can substitute for Rhomboid in two mutant flies with abnormalities in eye development and wing venation; conversely, Rhomboid can rescue aarA mutant bacteria and activate the expression of density-dependent genes. Using a transfected cell assay system, Urban et al. document the biochemical activities of a group of Rhomboid-like bacterial intramembrane serine proteases against the three transmembrane precursor ligands Spitz, Keren, and Gurken. — GJC

Proc. Natl. Acad. Sci. U.S.A.99, 12208 (2002); Curr. Biol.12, 1507 (2002).

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