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PLoS Negl Trop Dis ; 12(5): e0006493, 2018 05.
Article in English | MEDLINE | ID: mdl-29768419

ABSTRACT

Trichomonas vaginalis is a causative agent of Trichomoniasis, a leading non-viral sexually transmitted disease worldwide. In the current study, we show Heat shock protein 90 is essential for its growth. Upon genomic analysis of the parasite, it was found to possess seven ORFs which could potentially encode Hsp90 isoforms. We identified a cytosolic Hsp90 homolog, four homologs which can align to truncated cytosolic Hsp90 gene products along with two Grp94 homologs (ER isoform of Hsp90). However, both Grp94 orthologs lacked an ER retention motif. In cancer cells, it is very well established that Hsp90 is secreted and regulates key clients involved in metastases, migration, and invasion. Since Trichomonas Grp94 lacks ER retention motif, we examined the possibility of its secretion. By using cell biology and biochemical approaches we show that the Grp94 isoform of Hsp90 is secreted by the parasite by the classical ER-Golgi pathway. This is the first report of a genome encoded secreted Hsp90 in a clinically important parasitic protozoan.


Subject(s)
HSP90 Heat-Shock Proteins/metabolism , Protozoan Proteins/metabolism , Trichomonas Infections/parasitology , Trichomonas vaginalis/metabolism , Amino Acid Motifs , Cytosol/chemistry , Cytosol/metabolism , Endoplasmic Reticulum/genetics , Endoplasmic Reticulum/metabolism , Golgi Apparatus/genetics , Golgi Apparatus/metabolism , HSP90 Heat-Shock Proteins/chemistry , HSP90 Heat-Shock Proteins/genetics , Humans , Protein Transport , Protozoan Proteins/genetics , Trichomonas vaginalis/chemistry , Trichomonas vaginalis/classification , Trichomonas vaginalis/genetics
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