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 > School of Infection & Immunity |
| 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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