ArticleCellular microbiology2012
Ecotin-like serine peptidase inhibitor ISP1 of Leishmania major plays a role in flagellar pocket dynamics and promastigote differentiation.
Article in Cellular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Identification of a conserved gene family with an essential role inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-cell atlas ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Discovery of essential kinetoplastid-insect adhesion proteins and their function in Leishmania-sand fly interactions.Nature communications · 2024Article
- Ecotin: A versatile protease inhibitor of bacteria and eukaryotes.Frontiers in microbiology · 2023Review
- Role of the inhibitor of serine peptidase 2 (ISP2) of Trypanosoma brucei rhodesiense in parasite virulence and modulation of the inflammatory responses of the host.PLoS neglected tropical diseases · 2021Article
- Neutrophil elastase promotesFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Functional genomics in sand fly-derived Leishmania promastigotes.PLoS neglected tropical diseases · 2019Review
- Article
- Understanding Leishmania parasites through proteomics and implications for the clinic.Expert review of proteomics · 2018Review
- Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Article
- Shape, form, function andOpen biology · 2017Review
- Role of inhibitors of serine peptidases in protecting Leishmania donovani against the hydrolytic peptidases of sand fly midgut.Parasites & vectors · 2017Article
- Angiostrongylus cantonensis cathepsin B-like protease (Ac-cathB-1) is involved in host gut penetration.Parasite (Paris, France) · 2015Article
- Leishmania development in sand flies: parasite-vector interactions overview.Parasites & vectors · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Leishmania ISPs are ecotin-like natural peptide inhibitors of trypsin-family serine peptidases, enzymes that are absent from the Leishmania genome. This led to the proposal that ISPs inhibit host serine peptidases and we have recently shown that ISP2 inhibits neutrophil elastase, thereby enhancing parasite survival in murine macrophages. In this study we show that ISP1 has less serine peptidase inhibitory activity than ISP2, and in promastigotes both are generally located in the cytosol and along the flagellum. However, in haptomonad promastigotes there is a prominent accumulation of ISP1 and ISP2 in the hemidesmosome and for ISP2 on the cell surface. An L. major mutant deficient in all three ISP genes (Δisp1/2/3) was generated and compared with Δisp2/3 mutants to elucidate the physiological role of ISP1. In in vitro cultures, the Δisp1/2/3 mutant contained more haptomonad, nectomonad and leptomonad promastigotes with elongated flagella and reduced motility compared with Δisp2/3 populations, moreover it was characterized by very high levels of release of exosome-like vesicles from the flagellar pocket. These data suggest that ISP1 has a primary role in flagellar homeostasis, disruption of which affects differentiation and flagellar pocket dynamics.
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Registered trials
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