TY - JOUR
T1 - Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana
T2 - A potential glucose sensor
AU - Rodriguez-Contreras, Dayana
AU - Aslan, Hamide
AU - Feng, Xiuhong
AU - Tran, Khoa
AU - Yates, Phillip A.
AU - Kamhawi, Shaden
AU - Landfear, Scott M.
N1 - Publisher Copyright:
© FASEB.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 Δlmxgt1 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.
AB - 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 Δlmxgt1 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.
KW - Environmental sensing
KW - Leishmania parasites
KW - Protein expression
KW - TaV2A peptide
KW - Transceptor
UR - http://www.scopus.com/inward/record.url?scp=84937420345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937420345&partnerID=8YFLogxK
U2 - 10.1096/fj.14-251991
DO - 10.1096/fj.14-251991
M3 - Article
C2 - 25300620
AN - SCOPUS:84937420345
SN - 0892-6638
VL - 29
SP - 11
EP - 24
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -