title: Characterization of Drosophila aspartic proteases that induce the secretion of a Golgi-resident transferase, heparan sulfate 6-O-sulfotransferase.
abstract: Alzheimer's beta-secretase (BACE1), an aspartic protease, cleaves amyloid precursor protein to produce a neurotoxic peptide, amyloid-beta, which plays a role in triggering Alzheimer's disease. We previously found that BACE1 also cleaves a glycosyltransferase, alpha2,6-sialyltransferase, as a physiological substrate. In the present study, we performed a BLAST homology search, identified two Drosophila aspartic proteases that are homologous to human BACE1, and isolated their cDNAs. The proteins encoded by the cDNAs were designated as DASP1 and DASP2, which exhibited 59% and 50% similarity to human BACE1, respectively. Each protein contained a pair of active site motifs (Asp/Thr or Ser/Gly), which is a common characteristic of aspartic proteases including BACE1. Although DASP1 and DASP2 did not contain an apparent transmenbrane domain, the proteases overexpressed in COS cells were localized in the Golgi area. Some of the DASP1 overexpressed in S2 cells was secreted, but none of the DASP2 was. DASP1 transcripts were expressed in the head of fruitflies, whereas DASP2 transcripts were mainly expressed in the body. When either DASP1 or DASP2 was coexpressed together with a Golgi-resident transferase, Drosophila heparan sulfate 6-O-sulfotransferase, the protease enhanced the secretion of the transferase from the cells, indicating that both DASP1 and DASP2 can induce the secretion of the 6-O-sulfotransferase.
authors.affiliation: Glyco-chain Functions Laboratory, Frontier Research System, The Institute of Physical and Chemical Research, RIKEN, Wako, Saitama 351-0198.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kotani
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kamimura
authors.forename: Satomi
authors.initials: S
authors.lastname: Takeo
authors.forename: Toshiro
authors.initials: T
authors.lastname: Aigaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D010450:Endopeptidases; D017344:Genes, Insect; D006056:Golgi Apparatus / Q000201:enzymology* / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D015238:Sulfotransferases; C404189:heparan sulfate 6-O-sulfotransferase; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C503096:Bace protein, Drosophila; C503095:DASP1 protein, Drosophila; C509280:BACE1 protein, human