title: Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana: a potential glucose sensor.
abstract: In Leishmania mexicana parasites, a unique glucose transporter, LmxGT1, is selectively targeted to the flagellar membrane, suggesting a possible sensory role that is often associated with ciliary membrane proteins. Expression of LmxGT1 is down-regulated ∼20-fold by increasing cell density but is up-regulated ∼50-fold by depleting glucose from the medium, and the permease is strongly down-regulated when flagellated insect-stage promastigotes invade mammalian macrophages and transform into intracellular amastigotes. Regulation of LmxGT1 expression by glucose and during the lifecycle operates at the level of protein stability. Significantly, a ∆lmxgt1 null mutant, grown in abundant glucose, undergoes catastrophic loss of viability when parasites deplete glucose from the medium, a property not exhibited by wild-type or add-back lines. These results suggest that LmxGT1 may function as a glucose sensor that allows parasites to enter the stationary phase when they deplete glucose and that in the absence of this sensor, parasites do not maintain viability when they run out of glucose. However, alternate roles for LmxGT1 in monitoring glucose availability are considered. The absence of known sensory receptors with defined ligands and biologic functions in Leishmania and related kinetoplastid parasites underscores the potential significance of these observations.
authors.affiliation: Departments of Molecular Microbiology & Immunology and.
authors.forename: Dayana
authors.initials: D
authors.lastname: Rodriguez-Contreras
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hamide
authors.initials: H
authors.lastname: Aslan
authors.affiliation: Departments of Molecular Microbiology & Immunology and.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Feng
authors.affiliation: Departments of Molecular Microbiology & Immunology and.
authors.forename: Khoa
authors.initials: K
authors.lastname: Tran
authors.affiliation: Biochemistry & Molecular Biology, Oregon Health & Science University, Portland, Oregon, USA; and.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Yates
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Departments of Molecular Microbiology & Immunology and landfear@ohsu.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Landfear
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005407:Flagella / Q000378:metabolism; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007894:Leishmania mexicana / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011576:Psychodidae / Q000469:parasitology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D005947:Glucose
keywords: Leishmania parasites; TaV2A peptide; environmental sensing; protein expression; transceptor