title: Expression and characterization of Drosophila signal peptide peptidase-like (sppL), a gene that encodes an intramembrane protease.
abstract: Intramembrane proteases of the Signal Peptide Peptidase (SPP) family play important roles in developmental, metabolic and signaling pathways. Although vertebrates have one SPP and four SPP-like (SPPL) genes, we found that insect genomes encode one Spp and one SppL. Characterization of the Drosophila sppL gene revealed that the predicted SppL protein is a highly conserved structural homolog of the vertebrate SPPL3 proteases, with a predicted nine-transmembrane topology, an active site containing aspartyl residues within a transmembrane region, and a carboxy-terminal PAL domain. SppL protein localized to both the Golgi and ER. Whereas spp is an essential gene that is required during early larval stages and whereas spp loss-of-function reduced the unfolded protein response (UPR), sppL loss of function had no apparent phenotype. This was unexpected given that genetic knockdown phenotypes in other organisms suggested significant roles for Spp-related proteases.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Casso
authors.forename: Songmei
authors.initials: S
authors.lastname: Liu
authors.forename: Brian
authors.initials: B
authors.lastname: Biehs
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kornberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D020134:Catalytic Domain; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017344:Genes, Insect; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000201:enzymology; D056811:Unfolded Protein Response
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; D016282:Aspartic Acid Endopeptidases; C574210:SppL protein, Drosophila; C460085:signal peptide peptidase