title: Membrane-associated dipeptidyl peptidase IV is involved in encystation-specific gene expression during Giardia differentiation.
abstract: Giardia is a flagellated protozoan that resides in the upper small intestine of its vertebrate host and is the most common cause of defined waterborne diarrhoea worldwide. Giardia trophozoites undergo significant biological changes to survive outside the host by differentiating into infective cysts. Encystation is thus essential for transmission of the parasite among susceptible hosts. In the present study, we report that bestatin, a competitive inhibitor of aminopeptidases, blocks cyst formation in vitro by abolishing the expression of encystation-specific genes, such as those coding for cyst wall proteins. Bestatin does not affect proliferating trophozoites, indicating that its effect is encystation-specific. Using biochemical and molecular biological approaches, we identified the enzyme inhibited by bestatin and cloned its corresponding gene. Sequence similarity indicated that this enzyme belongs to a family of dipeptidyl peptidases. Our results suggest that a specific proteolytic event caused by a constitutively expressed membrane-associated dipeptidyl peptidase IV is necessary for encystation of Giardia.
authors.affiliation: Catedra de Bioquimica y Biologia Molecular, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba. CP 5000. Cordoba, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Touz
authors.forename: María J
authors.initials: MJ
authors.lastname: Nores
authors.forename: Ileana
authors.initials: I
authors.lastname: Slavin
authors.forename: Lucía
authors.initials: L
authors.lastname: Piacenza
authors.forename: Daniel
authors.initials: D
authors.lastname: Acosta
authors.forename: Carlos
authors.initials: C
authors.lastname: Carmona
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Luján
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D003001:Cloning, Molecular; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D005872:Giardia / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D018819:Dipeptidyl Peptidase 4; D007930:Leucine; C012211:ubenimex