KHARON Is an essential cytoskeletal protein involved in the trafficking of flagellar membrane proteins and cell division in African trypanosomes

Sanchez, M. A., Tran, K. D., Valli, J., Hobbs, S., Johnson, E., Gluenz, E. and Landfear, S. M. (2016) KHARON Is an essential cytoskeletal protein involved in the trafficking of flagellar membrane proteins and cell division in African trypanosomes. Journal of Biological Chemistry, 291(38), pp. 19760-19773. (doi: 10.1074/jbc.M116.739235) (PMID:27489106) (PMCID:PMC5025667)

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Abstract

African trypanosomes and related kinetoplastid parasites selectively traffic specific membrane proteins to the flagellar membrane, but the mechanisms for this trafficking are poorly understood. We show here that KHARON, a protein originally identified in Leishmania parasites, interacts with a putative trypanosome calcium channel and is required for its targeting to the flagellar membrane. KHARON is located at the base of the flagellar axoneme, where it likely mediates targeting of flagellar membrane proteins, but is also on the subpellicular microtubules and the mitotic spindle. Hence, KHARON is probably a multifunctional protein that associates with several components of the trypanosome cytoskeleton. RNA interference-mediated knockdown of KHARON mRNA results in failure of the calcium channel to enter the flagellar membrane, detachment of the flagellum from the cell body, and disruption of mitotic spindles. Furthermore, knockdown of KHARON mRNA induces a lethal failure of cytokinesis in both bloodstream (mammalian host) and procyclic (insect vector) life cycle stages, and KHARON is thus critical for parasite viability.

Item Type:Articles
Additional Information:This work was supported, in whole or in part, by National Institutes of Health Grants R21-AI114822 and R01-AI121160 (to S. M. L.). This work was also supported by Biotechnology and Biological Sciences Research Council Grant BB/C014122/1 and Shared Instrumentation Grant S10-RR023432 from the National Center for Research Resources, a component of the National Institutes of Health.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gluenz, Dr Eva
Authors: Sanchez, M. A., Tran, K. D., Valli, J., Hobbs, S., Johnson, E., Gluenz, E., and Landfear, S. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
ISSN (Online):1083-351X
Published Online:03 August 2016
Copyright Holders:Copyright © 2016 by The American Society for Biochemistry and Molecular Biology, Inc
First Published:First published in Journal of Biological Chemistry 291(38):19760-19773
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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