AI Article Synopsis
- Leishmania secretes many effectors, but the regulation of its secretory pathway is not well understood; this study focuses on the cloning and characterization of LdRab1, a Rab1 homologue.
- LdRab1 localizes in the Golgi of Leishmania, and experiments with transgenic parasites reveal that overexpressing certain mutants of LdRab1 does not affect hemoglobin receptor trafficking but significantly inhibits the secretion of proteins like secretory acid phosphatase and Ldgp63.
- The findings indicate that while the Rab1-regulated secretory pathway is conserved in Leishmania, hemoglobin receptor trafficking operates through a different, Rab1-independent pathway.
Article Abstract
Leishmania secretes a large number of its effectors to the extracellular milieu. However, regulation of the secretory pathway in Leishmania is not well characterized. Here, we report the cloning, expression, and characterization of the Rab1 homologue from Leishmania. We have found that LdRab1 localizes in Golgi in Leishmania. To understand the role of LdRab1 in the secretory pathway of Leishmania, we have generated transgenic parasites overexpressing GFP-LdRab1:WT, GFP-LdRab1:Q67L (a GTPase-deficient dominant positive mutant of Rab1), and GFP-LdRab1:S22N (a GDP-locked dominant negative mutant of Rab1). Surprisingly, our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N does not disrupt the trafficking and localization of hemoglobin receptor in Leishmania. To determine whether the Rab1-dependent secretory pathway is conserved in parasites, we have analyzed the role of LdRab1 in the secretion of secretory acid phosphatase and Ldgp63 in Leishmania. Our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N significantly inhibits the secretion of secretory acid phosphatase by Leishmania. We have also found that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N retains RFP-Ldgp63 in Golgi and blocks the secretion of Ldgp63, whereas the trafficking of RFP-Ldgp63 in GFP-LdRab1:WT-expressing cells is unaltered in comparison with control cells. Taken together, our results have shown that the Rab1-regulated secretory pathway is well conserved, and hemoglobin receptor trafficking follows an Rab1-independent secretory pathway in Leishmania.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706007 | PMC |
| http://dx.doi.org/10.1074/jbc.M115.670018 | DOI Listing |
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