The Trypanosoma brucei TbHrg protein is a heme transporter involved in the regulation of stage-specific morphological transitions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F17%3A00479119" target="_blank" >RIV/60077344:_____/17:00479119 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/17:00479119 RIV/60076658:12310/17:43895458
Result on the web
<a href="http://dx.doi.org/10.1074/jbc.M116.762997" target="_blank" >http://dx.doi.org/10.1074/jbc.M116.762997</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1074/jbc.M116.762997" target="_blank" >10.1074/jbc.M116.762997</a>
Alternative languages
Result language
angličtina
Original language name
The Trypanosoma brucei TbHrg protein is a heme transporter involved in the regulation of stage-specific morphological transitions
Original language description
The human parasite Trypanosoma brucei does not synthesize heme de novo and instead relies entirely on heme supplied by its vertebrate host or its insect vector, the tsetse fly. In the host bloodstream T. brucei scavenges heme via haptoglobin-hemoglobin (HpHb) receptor-mediated endocytosis occurring in the flagellar pocket. However, in the procyclic developmental stage, in which T. brucei is confined to the tsetse fly midgut, this receptor is apparently not expressed, suggesting that T. brucei takes up heme by a different, unknown route. To define this alternative route, we functionally characterized heme transporter TbHrg in the procyclic stage. RNAi-induced down-regulation of TbHrg in heme-limited culture conditions resulted in slower proliferation, decreased cellular heme, and marked changes in cellular morphology so that the cells resemble mesocyclic trypomastigotes. Nevertheless, the TbHrg KO developed normally in the tsetse flies at rates comparable with wild-type cells. T. brucei cells overexpressing TbHrg displayed up-regulation of the early procyclin GPEET and down-regulation of the late procyclin EP1, two proteins coating the T. brucei surface in the procyclic stage. Light microscopy of immunostained TbHrg indicated localization to the flagellar membrane, and scanning electron microscopy revealed more intense TbHrg accumulation toward the flagellar pocket. Based on these findings, we postulate that T. brucei senses heme levels via the flagellar TbHrg protein. Heme deprivation in the tsetse fly anterior midgut might represent an environmental stimulus involved in the transformation of this important human parasite, possibly through metabolic remodeling.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA16-18699S" target="_blank" >GA16-18699S: Heme: a putative master regulator in trypanosomatids</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Biological Chemistry
ISSN
0021-9258
e-ISSN
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Volume of the periodical
292
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
6998-7010
UT code for WoS article
000400478300012
EID of the result in the Scopus database
2-s2.0-85018346018