title: Identification of a family of four UDP-polypeptide N-acetylgalactosaminyl transferases in Cryptosporidium species.
abstract: Although mucin-type O-glycans are critical for Cryptosporidium infection, the enzymes catalyzing their synthesis have not been studied. Here, we report four UDP N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyl transferases (ppGalNAc-Ts) from the genomes of C. parvum, C. hominis and C. muris. All are Type II membrane proteins which include a cytoplasmic tail, a transmembrane domain, a stem region, a glycosyltransferase family 2 domain and a C-terminal ricin B lectin domain. All are expressed during C. parvum infection in vitro, with Cp-ppGalNAc-T1 and -T4 expressed at 24 h and Cp-ppGalNAc-T2 and -T3 at 48 and 72 h post-infection, suggesting that their expression may be developmentally regulated. C. parvum sporozoite lysates display ppGalNAc-T enzymatic activity against non-glycosylated and pre-glycosylated peptides suggesting that they contain enzymes capable of glycosylating both types of substrates. The importance of mucin-type O-glycans in Cryptosporidium-host cell interactions raises the possibility that Cp-ppGalNAc-Ts may serve as targets for intervention in cryptosporidiosis.
authors: Tufts Medical Center, Boston, MA, United States.
authors: Najma
authors: N
authors: Bhat
authors: Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, United States.
authors: Boguslaw S
authors: BS
authors: Wojczyk
authors: Tufts Medical Center, Boston, MA, United States.|Tufts University Sackler School of Graduate Medical Sciences, Boston, MA, United States.
authors: Maria
authors: M
authors: DeCicco
authors: University of Puerto Rico, Cayey, PR, United States.
authors: Carlos
authors: C
authors: Castrodad
authors: Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, United States.
authors: Steven L
authors: SL
authors: Spitalnik
authors: Tufts Medical Center, Boston, MA, United States.|Tufts University Sackler School of Graduate Medical Sciences, Boston, MA, United States.
authors: Honorine D
authors: HD
authors: Ward
mesh_terms: D003458:Cryptosporidium / Q000201:enzymology* / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D016054:DNA, Protozoan; D008565:Membrane Proteins; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: Cryptosporidium; Mucin; Mucin-like glycoprotein; O-glycosylation; UDP GalNAc:polypeptide N-acetylgalactosaminyl transferase
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