Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana: A potential glucose sensor

Dayana Rodriguez-Contreras, Hamide Aslan, Xiuhong Feng, Khoa Tran, Phillip Yates, Shaden Kamhawi, Scott Landfear

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)11-24
Number of pages14
JournalFASEB Journal
Volume29
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Glucose sensors
Facilitative Glucose Transport Proteins
Glucose
Parasites
Leishmania mexicana
Membrane Transport Proteins
Protein Stability
Macrophages
Leishmania
Sensory Receptor Cells
Leishmania glucose transporter
Insects
Membrane Proteins
Cell Count
Availability
Ligands
Membranes
Monitoring
Sensors

Keywords

  • Environmental sensing
  • Leishmania parasites
  • Protein expression
  • TaV2A peptide
  • Transceptor

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana : A potential glucose sensor. / Rodriguez-Contreras, Dayana; Aslan, Hamide; Feng, Xiuhong; Tran, Khoa; Yates, Phillip; Kamhawi, Shaden; Landfear, Scott.

In: FASEB Journal, Vol. 29, No. 1, 01.01.2015, p. 11-24.

Research output: Contribution to journalArticle

Rodriguez-Contreras, Dayana ; Aslan, Hamide ; Feng, Xiuhong ; Tran, Khoa ; Yates, Phillip ; Kamhawi, Shaden ; Landfear, Scott. / Regulation and biological function of a flagellar glucose transporter in Leishmania mexicana : A potential glucose sensor. In: FASEB Journal. 2015 ; Vol. 29, No. 1. pp. 11-24.
@article{9dab7c46b43e4524af90ae4f1cef9f04,
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 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.",
keywords = "Environmental sensing, Leishmania parasites, Protein expression, TaV2A peptide, Transceptor",
author = "Dayana Rodriguez-Contreras and Hamide Aslan and Xiuhong Feng and Khoa Tran and Phillip Yates and Shaden Kamhawi and Scott Landfear",
year = "2015",
month = "1",
day = "1",
doi = "10.1096/fj.14-251991",
language = "English (US)",
volume = "29",
pages = "11--24",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",

}

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

AU - Kamhawi, Shaden

AU - Landfear, Scott

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

VL - 29

SP - 11

EP - 24

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 1

ER -