RRC ID 6418
著者 Novelli JF, Chaudhary K, Canovas J, Benner JS, Madinger CL, Kelly P, Hodgkin J, Carlow CK.
タイトル Characterization of the Caenorhabditis elegans UDP-galactopyranose mutase homolog glf-1 reveals an essential role for galactofuranose metabolism in nematode surface coat synthesis.
ジャーナル Dev Biol
Abstract Galactofuranose (Gal(f)), the furanoic form of d-galactose produced by UDP-galactopyranose mutases (UGMs), is present in surface glycans of some prokaryotes and lower eukaryotes. Absence of the Gal(f) biosynthetic pathway in vertebrates and its importance in several pathogens make UGMs attractive drug targets. Since the existence of Gal(f) in nematodes has not been established, we investigated the role of the Caenorhabditis elegans UGM homolog glf-1 in worm development. glf-1 mutants display significant late embryonic and larval lethality, and other phenotypes indicative of defective surface coat synthesis, the glycan-rich outermost layer of the nematode cuticle. The glf homolog from the protozoan Leishmania major partially complements C. elegans glf-1. glf-1 mutants rescued by L. major glf, which behave as glf-1 hypomorphs, display resistance to infection by Microbacterium nematophilum, a pathogen of rhabditid nematodes thought to bind to surface coat glycans. To confirm the presence of Gal(f) in C. elegans, we analyzed C. elegans nucleotide sugar pools using online electrospray ionization-mass spectrometry (ESI-MS). UDP-Gal(f) was detected in wild-type animals while absent in glf-1 deletion mutants. Our data indicate that Gal(f) likely has a pivotal role in maintenance of surface integrity in nematodes, supporting investigation of UGM as a drug target in parasitic species.
巻・号 335(2)
ページ 340-55
公開日 2009-11-15
DOI 10.1016/j.ydbio.2009.09.010
PII S0012-1606(09)01179-8
PMID 19751718
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Caenorhabditis elegans / enzymology* Caenorhabditis elegans / metabolism Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / biosynthesis* Galactose / metabolism* Gene Knockout Techniques Gram-Positive Bacteria / pathogenicity Intramolecular Transferases / chemistry Intramolecular Transferases / genetics Intramolecular Transferases / metabolism* Molecular Sequence Data Sequence Homology, Amino Acid Spectrometry, Mass, Electrospray Ionization
IF 2.896
引用数 29
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm2621 tm2412