Micchelli, Craig A.The, IngeSelva, EricaMoglia, VladicPerrimon, Norbert2021-04-05Micchelli, Craig A., Erica Selva, Vladic Mogila, and Norbert Perrimon. "Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling." Development 129, no. 4 (2002): 843-851.https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37367166Members of the Hedgehog (Hh) family encode secreted molecules that act as potent organizers during vertebrate and invertebrate development. Post-translational modification regulates both the range and efficacy of Hh protein. One such modification is the acylation of the N- terminal cysteine of Hh. In a screen for zygotic lethal mutations associated with maternal effects, we have identified rasp, a novel Drosophila segment polarity gene. Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. The requirement of rasp is restricted only to those cells that produce Hh; hh transcription, protein levels and distribution are not affected by the loss of rasp. Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein.en-USJournal Article2021-04-05