Ecotin-like serine peptidase inhibitor ISP1 of Leishmania major plays a role in flagellar pocket dynamics and promastigote differentiation

Morrison, L. S. et al. (2012) Ecotin-like serine peptidase inhibitor ISP1 of Leishmania major plays a role in flagellar pocket dynamics and promastigote differentiation. Cellular Microbiology, 14(8), pp. 1271-1286. (doi: 10.1111/j.1462-5822.2012.01798.x)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Morrison, Dr Lesley and Coombs, Professor Graham and Tetley, Dr Laurence and Westrop, Mr Gareth and Eschenlauer, Dr Sylvain and Mottram, Professor Jeremy
Authors: Morrison, L. S., Goundry, A., Faria, M. S., Tetley, L., Eschenlauer, S. C., Westrop, G. D., Dostalova, A., Volf, P., Coombs, G. H., Lima, A. P. C.A., and Mottram, J. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Cellular Microbiology
Publisher:Wiley-Blackwell Publishing
ISSN (Online):1462-5822
Published Online:08 May 2012
Copyright Holders:Copyright © 2012 Blackwell Publishing Ltd.
First Published:First published in Cellular Microbiology 14(8):1271-1286
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
454141Analysing the roles of petidases in Leishmania infectivity and pathogenicityJeremy MottramMedical Research Council (MRC)G0700127III - BACTERIOLOGY
447361Natural peptidase inhibitors of trypanosomatidsJeremy MottramWellcome Trust (WELLCOME)081877/Z/06/ZIII - BACTERIOLOGY