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Disruption of the fusion of Leishmania parasitophorous vacuoles with ER vesicles results in the control of the infection

Canton, Johnathan and Ndjamen, Blaise and Hatsuzawa, Kiyotaka and Kima, Peter E. (2012) Disruption of the fusion of Leishmania parasitophorous vacuoles with ER vesicles results in the control of the infection. Cellular Microbiology, 14 (6). pp. 937-948. ISSN 1462-5814. doi:10.1111/j.1462-5822.2012.01767.x. https://resolver.caltech.edu/CaltechAUTHORS:20120614-103008693

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Abstract

Parasitophorous vacuoles (PV) that harbour Leishmania parasites acquire some characteristics from fusion with host cell vesicles. Recent studies have shown that PVs acquire and display resident endoplasmic reticulum (ER) molecules. We investigated the importance of ER molecules to PV biology by assessing the consequence of blocking the fusion of PVs with vesicles that originate from the early secretory pathway. This was achieved by targeting the N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) that mediate the fusion of early secretory vesicles. In the presence of dominant negative variants of sec22b or some of its known cognate partners, D12 and syntaxin 18, PVs failed to distend and harboured fewer parasites. These observations were confirmed in studies in which each of the SNAREs listed above including the intermediate compartment ER/Golgi SNARE, syntaxin 5, was knocked down. The knock-down of these SNARES had little or no measurable effect on the morphology of the ER or on activated secretion even though they resulted in a more significant reduction of PV size. Moreover, the knock-down of the ER/Golgi SNAREs resulted in significant reduction in parasite replication. Taken together, these studies provide further evidence that PVs acquire ER components by fusing with vesicles derived from the early secretory pathway; disruption of this interaction results in inhibition of the development of PVs as well as the limitation of parasite replication within infected cells.


Item Type:Article
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http://dx.doi.org/10.1111/j.1462-5822.2012.01767.xDOIUNSPECIFIED
http://onlinelibrary.wiley.com/doi/10.1111/j.1462-5822.2012.01767.x/abstractPublisherUNSPECIFIED
Additional Information:© 2012 Blackwell Publishing Ltd. Issue published online: 16 May 2012; Article first published online: 24 Feb 2012; Accepted manuscript online: 6 Feb 2012; Received 16 August, 2011; revised 12 January, 2012; accepted 19 January, 2012. These studies were supported in part by NIH R01 funds and funds from the University of Florida Foundation. The authors have no conflict of interest.
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Funding AgencyGrant Number
NIH R01 FundsUNSPECIFIED
University of Florida FoundationUNSPECIFIED
Issue or Number:6
DOI:10.1111/j.1462-5822.2012.01767.x
Record Number:CaltechAUTHORS:20120614-103008693
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120614-103008693
Official Citation:Canton, J., Ndjamen, B., Hatsuzawa, K. and Kima, P. E. (2012), Disruption of the fusion of Leishmania parasitophorous vacuoles with ER vesicles results in the control of the infection. Cellular Microbiology, 14: 937–948. doi: 10.1111/j.1462-5822.2012.01767.x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:31898
Collection:CaltechAUTHORS
Deposited By: Aucoeur Ngo
Deposited On:18 Jun 2012 20:10
Last Modified:09 Nov 2021 20:02

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