biostudies-literature00460Rodriguez-Contreras DNational Institute of Allergy and Infectious DiseasesIntramural NIH HHSNational Center for Research ResourcesNCRR NIH HHSNIAID NIH HHSNational Institutes of Health11-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC4285543biostudies-literatureUnknown29(1)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.FASEB journal : official publication of the Federation of American Societies for Experimental BiologyRegulation and biological function of a flagellar glucose transporter in Leishmania mexicana: a potential glucose sensor.PMC4285543S10-RR023432R37 AI023682S10 RR023432AI023682R01 AI025920S10‐RR023432F32 AI096854AI25920R01 AI023682Rodriguez-Contreras DFeng XKamhawi SLandfear SMYates PATran KAslan H46falseRegulation and biological function of a flagellar glucose transporter in Leishmania mexicana: a potential glucose sensor.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.2015-01-01T00:00:00Z2015 Jan2024-11-13T01:02:33.403Z2019-03-26T23:55:41ZS-EPMC42855432530062010.1096/fj.14-251991