Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters

Deqin Ma; David G Russell; Stephen M Beverley; Salvatore J Turco

doi:10.1074/jbc.272.6.3799

Back

Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters

Journal article

Open access

Peer reviewed

Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters

Deqin Ma, David G Russell, Stephen M Beverley and Salvatore J Turco

The Journal of biological chemistry, Vol.272(6), pp.3799-3805

02/07/1997

DOI: 10.1074/jbc.272.6.3799

PMID: 9013638

Files and links (1)

url

https://doi.org/10.1074/jbc.272.6.3799View

Published (Version of record) Open Access

Abstract

The synthesis of glycoconjugates within the secretory pathway of eukaryotes requires the provision of lumenal nucleotide-sugar substrates. This is particularly important for eukaryotic microbes such as Leishmania because they must synthesize considerable amounts of extracellular and cell surface glycoconjugates that play significant roles in the infectious cycle. Here we used properly oriented sealed microsomes to characterize lumenal uptake of GDP-Man in Leishmania donovani. In this system, GDP-Man uptake was saturable with an apparent Km for GDP-Man of 0.3 microM and facilitated its use as a donor substrate for lipophosphoglycan (LPG) synthesis. A lpg2(-) deletion mutant showed loss of GDP-Man but not UDP-Gal uptake, which was restored by introduction of the gene LPG2. Immunoelectron microscopy localized an active, epitope-tagged LPG2 protein to the Golgi apparatus. Thus, LPG2 is required for nucleotide-sugar transport activity and probably encodes this Golgi transporter. LPG2 belongs to a large family of eukaryotic genes that potentially encode transporters with different substrate specificities and/or cellular locations. In the future, the amenability of the Leishmania system to biochemical and genetic manipulation will assist in functional characterization of nucleotide-sugar transports from this and other eukaryotes. Furthermore, since LPG2 plays an important role in the Leishmania infectious cycle and mammalian cells lack a Golgi GDP-Man transporter, this activity may offer a new target for chemotherapy.

Transfection

Amino Acid Sequence

Microsomes - metabolism

Leishmania donovani

Molecular Sequence Data

Chromatography, Thin Layer

Sequence Alignment

Animals

Protozoan Proteins - metabolism

Glycosphingolipids - metabolism

Golgi Apparatus - metabolism

Membrane Proteins - metabolism

Guanosine Diphosphate Mannose - metabolism

Details

Title: Subtitle: Golgi GDP-mannose uptake requires Leishmania LPG2. A member of a eukaryotic family of putative nucleotide-sugar transporters
Creators: Deqin Ma - Department of Biochemistry, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA
David G Russell
Stephen M Beverley
Salvatore J Turco
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.272(6), pp.3799-3805
DOI: 10.1074/jbc.272.6.3799
PMID: 9013638
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: AI31078 / NIAID NIH HHS
Language: English
Date published: 02/07/1997
Academic Unit: Pathology
Record Identifier: 9984046902502771

Metrics

18 Record Views

139 Times Cited - Web of Science