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Functional redundancy of Caenorhabditis elegans nucleotide‐sugar transporters
Author(s) -
Caffaro Carolina Edith,
Hirschberg Carlos,
Berninsone Patricia
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a55
Subject(s) - caenorhabditis elegans , biology , mutant , complementation , microbiology and biotechnology , phenotype , gene , genetics , genetic screen , biochemistry
There are several examples of the pathophysiological relevance of nucleotide‐sugar transporters (NSTs) in yeast, protozoal parasites, C.elegans and mammals. Nevertheless, the physiological roles of NSTs may be hampered by redundant gene function. C.elegans is a genetically and developmentally well characterized organism for which only 2 out of 16 NST‐like proteins have been described. In the present work, C03H5.2 –a cDNA encoding a putative NST‐ was functionally expressed in S.cerevisiae. The corresponding Golgi vesicle enriched fraction transported UDP‐GalNAc and UDP‐GlcNAc in a temperature‐dependent and saturable manner. UDP‐GlcNAc transport activity was also demonstrated in vivo by complementation of a Kluyveromyces lactis mutant defective in this transport. Inactivation of C03H5.2 in wild type worms by RNAi didn’t show any visual phenotype. Srf‐3, a previously described NST in C.elegans also has UDP‐GlcNAc transport activity and srf‐3 mutants have a very mild visual phenotype. Therefore, a possible biochemical redundancy in this activity was investigated. Inactivation of C03H5.2 by RNAi in srf‐3 mutants showed a striking phenotype characterized by abnormal positions of eggs, oocyte accumulation and body constriction. Moreover, transgenic animals for C03H5.2 promoter::GFP fusion were examined and compared to the expression pattern of srf‐3, a partial overlapping localization was revealed. This provides the first evidence for biochemical redundancy of NSTs in any organism and constitutes a starting point to understand regulation of these transporters in multicellular organisms. NIH –GM30365