scholarly journals The Trypanosoma brucei Cytoskeletal Protein KHARON Associates with Partner Proteins to Mediate Both Cytokinesis and Trafficking of Flagellar Membrane Proteins

2020 ◽  
Author(s):  
Marco A. Sanchez ◽  
Scott M. Landfear
Keyword(s):  
Membrane Proteins ◽  
Trypanosoma Brucei ◽  
Tsetse Fly ◽  
Cytoskeletal Protein ◽  
Close Proximity ◽  
Flagellar Membrane ◽  
Parasite Viability ◽  
Parasite Biology ◽  
Partner Proteins ◽  
Core Activity

ABSTRACTIn the African trypanosome Trypanosoma brucei, the cytoskeletal protein TbKHARON is required for trafficking of a putative Ca2+ channel to the flagellar membrane, and it is essential for parasite viability in both the mammalian stage bloodstream forms and the tsetse fly procyclic forms. This protein is located at the base of the flagellum, in the pellicular cytoskeleton, and in the mitotic spindle in both life cycle forms, and it likely serves multiple functions for these parasites. To begin to deconvolve the functions of KHARON, we have investigated partners associated with this protein and their roles in parasite biology. One KHARON associated protein, TbKHAP1, is a close interaction partner that can be crosslinked to KHARON by formaldehyde and pulled down in a molecular complex, and it colocalizes with TbKHARON in the basal body at the base of the flagellum. Knockdown of TbKHAP1 mRNA has similar phenotypes to knockdown of its partner TbKHARON, impairing trafficking of the Ca2+ channel to the flagellar membrane and blocking cytokinesis, implying that the TbKHARON/TbKHAP1 complex mediates trafficking of flagellar membrane proteins. Two other KHAPs, TbKHAP2 and TbKHAP3, are in close proximity to TbKHARON, but knockdown of their mRNAs does not affect trafficking of the Ca2+ channel. Two different flagellar membrane proteins, which are extruded from the flagellar membrane into extracellular vesicles, are also dependent upon TbKHARON for flagellar trafficking. These studies confirm that TbKHARON acts in complexes with other proteins to carry out various biological functions, and that some partners are involved in the core activity of targeting membrane proteins to the flagellum.

scholarly journals A Cytoskeletal Protein Complex is Essential for Division of Intracellular Amastigotes of Leishmania mexicana

2020 ◽  
Author(s):  
Felice D. Kelly ◽  
Khoa D. Tran ◽  
Jess Hatfield ◽  
Kat Schmidt ◽  
Marco A. Sanchez ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Protein Complex ◽  
Mitotic Spindle ◽  
Glucose Transporter ◽  
Cytoskeletal Protein ◽  
Leishmania Mexicana ◽  
Intracellular Amastigotes ◽  
Flagellar Membrane ◽  
Partner Proteins ◽  
Null Mutants

AbstractPrevious studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, that associate with KHARON. KHAP1 is located only in the subpellicular microtubules, while KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both the KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.

scholarly journals A cytoskeletal protein complex is essential for division of intracellular amastigotes of Leishmania mexicana

2020 ◽  
Vol 295 (37) ◽  
pp. 13106-13122 ◽  
Author(s):  
Felice D. Kelly ◽  
Khoa D. Tran ◽  
Jess Hatfield ◽  
Kat Schmidt ◽  
Marco A. Sanchez ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Protein Complex ◽  
Mitotic Spindle ◽  
Glucose Transporter ◽  
Cytoskeletal Protein ◽  
Leishmania Mexicana ◽  
Intracellular Amastigotes ◽  
Flagellar Membrane ◽  
Partner Proteins ◽  
Null Mutants

Previous studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, which associate with KHARON. KHAP1 is located only in the subpellicular microtubules, whereas KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.

scholarly journals KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of Flagellar Membrane Proteins and Cell Division in African Trypanosomes

2016 ◽  
Vol 291 (38) ◽  
pp. 19760-19773 ◽  
Author(s):  
Marco A. Sanchez ◽  
Khoa D. Tran ◽  
Jessica Valli ◽  
Sam Hobbs ◽  
Errin Johnson ◽  
...  
Keyword(s):  
Cell Division ◽  
Membrane Proteins ◽  
Cytoskeletal Protein ◽  
African Trypanosomes ◽  
Flagellar Membrane

scholarly journals Metabolic reprogramming during the Trypanosoma brucei life cycle

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 683 ◽  
Author(s):  
Terry K. Smith ◽  
Frédéric Bringaud ◽  
Derek P. Nolan ◽  
Luisa M. Figueiredo
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Model Organism ◽  
Protozoan Parasite ◽  
Tsetse Fly ◽  
Metabolic Reprogramming ◽  
Mammalian Host ◽  
Insect Vector ◽  
Environmental Signals ◽  
Cellular Metabolic Activity

Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

scholarly journals The Double-Edged Sword in Pathogenic Trypanosomatids: The Pivotal Role of Mitochondria in Oxidative Stress and Bioenergetics

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Rubem Figueiredo Sadok Menna-Barreto ◽  
Solange Lisboa de Castro
Keyword(s):  
Trypanosoma Brucei ◽  
Cell Signalling ◽  
Oxygen Species ◽  
Kinetoplast Dna ◽  
Excellent Candidate ◽  
Causative Agents ◽  
Parasite Biology ◽  
Oxidative Regulation ◽  
Single Mitochondrion

The pathogenic trypanosomatidsTrypanosoma brucei,Trypanosoma cruzi, andLeishmaniaspp. are the causative agents of African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific arrangement of mitochondrial DNA (kinetoplast DNA). Due to mitochondrial differences between mammals and trypanosomatids, this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids’ life cycle, the shape and functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments. In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatid-targeting chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.

Trypanosoma brucei: posttranscriptional control of the variable surface glycoprotein gene expression site

1989 ◽  
Vol 9 (9) ◽  
pp. 4018-4021
Author(s):  
E Pays ◽  
H Coquelet ◽  
A Pays ◽  
P Tebabi ◽  
M Steinert
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Transcription Initiation ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Insect Vector ◽  
Variable Surface Glycoprotein ◽  
A Genome ◽  
Variable Surface ◽  
Expression Site

The arrest of variable surface glycoprotein (VSG) synthesis is one of the first events accompanying the differentiation of Trypanosoma brucei bloodstream forms into procyclic forms, which are characteristic of the insect vector. This is because of a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered. We report that this effect is probably not controlled at the level of transcription initiation, since the beginning of the VSG gene expression site, about 45 kilobases upstream from the antigen gene, remains transcribed in procyclic forms. The permanent activity of the promoter readily accounts for the systematic reappearance, upon return to the bloodstream form after cyclical transmission, of the antigen type present before passage to the tsetse fly. The abortive transcription of the VSG gene expression site appears linked to RNA processing abnormalities. Such posttranscriptional controls may allow the modulation of gene expression in a genome organized in large multigenic transcription units.

scholarly journals Differential virulence and tsetse fly transmissibility of Trypanosoma congolense and Trypanosoma brucei strains

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Purity K. Gitonga ◽  
Kariuki Ndung’u ◽  
Grace A. Murilla ◽  
Paul C. Thande ◽  
Florence N. Wamwiri ◽  
...  
Keyword(s):  
Survival Time ◽  
Trypanosoma Brucei ◽  
Acute Infection ◽  
Glossina Pallidipes ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Economic Losses ◽  
Entire Group ◽  
Tsetse Flies ◽  
African Countries

African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.). In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6). We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates. Results showed that the overall pre-patent (PP) periods were 8.4 ± 0.9 (range, 4–11) and 4.5 ± 0.2 (range, 4–6) for T. congolense and T. brucei isolates, respectively (p < 0.01). Despite the longer mean PP, T. congolense–infected mice exhibited a significantly (p < 0.05) shorter survival time than T. brucei–infected mice, indicating greater virulence. Differences were also noted among the individual isolates with T. congolense KETRI 2909 causing the most acute infection of the entire group with a mean ± standard error survival time of 9 ± 2.1 days. Survival time of infected tsetse flies and the proportion with mature infections at 30 days post-exposure to the infective blood meals varied among isolates, with subacute infection–causing T. congolense EATRO 1829 and chronic infection–causing T. brucei EATRO 2267 isolates showing the highest mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study provides further evidence of occurrence of differences in virulence and transmissibility of eastern African trypanosome strains and has identified two, T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse infectivity and transmissibility experiments.

scholarly journals Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Harriet Lane-Serff ◽  
Paula MacGregor ◽  
Lori Peacock ◽  
Olivia JS Macleod ◽  
Christopher Kay ◽  
...  
Keyword(s):  
Developmental Stage ◽  
Trypanosoma Brucei ◽  
Evolutionary History ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Trypanosome Species ◽  
African Trypanosome ◽  
Evolutionary Diversification ◽  
Cellular Changes

The haptoglobin-haemoglobin receptor of the African trypanosome species, Trypanosoma brucei, is expressed when the parasite is in the bloodstream of the mammalian host, allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes. Here we show that in Trypanosoma congolense this receptor is instead expressed in the epimastigote developmental stage that occurs in the tsetse fly, where it acts as a haemoglobin receptor. We also present the structure of the T. congolense receptor in complex with haemoglobin. This allows us to propose an evolutionary history for this receptor, charting the structural and cellular changes that took place as it adapted from a role in the insect to a new role in the mammalian host.

scholarly journals A peridomestic population of the tsetse fly Glossina palpalis palpalis Robineau-Desvoidy, 1830 (Diptera: Glossinidae) at Kontagora town, Niger state, Nigeria

2004 ◽  
Vol 11 (4) ◽  
pp. 599-610 ◽  
Author(s):  
A. B. Ahmed
Keyword(s):  
Tsetse Fly ◽  
Glossina Palpalis Palpalis ◽  
Infection Rates ◽  
Wet Season ◽  
Abnormal Behaviour ◽  
The Public ◽  
Close Proximity ◽  
Reservoir Hosts ◽  
Glossina Palpalis ◽  
Wild Life

The present article considers some aspects of a peridomestic population of the tsetse fly Glossina palpalis palpalis Robineau-Desvoidy, 1830 in Kontagora, Nigeria. This situation characterizes an abnormal behaviour of the vector, and it is of significant epidemiological importance. Data on the ecology of this species were collected in 1995 and 1999. The results indicated that the species exists during both dry and wet seasons; approximately 30.0% of the catches were gorged with blood giving a MHS of 2.4, indicating a well-nourished population. Dissection of inseminated pars indicated pregnancy rates of approximately 30.0% and 70.0% in the dry and wet seasons and the presence of all 4 stages of pregnancy, suggesting that breeding occurs at both seasons. Longevity of flies was approximately 16 days in dry season and 25 days in the wet season. Overall results indicated that vector/host contact was high and the fly population has adapted and actively breeding in the area. Trypanosome infection rates of 18.2% consist of 1 brucei-type and 5 vivax-type infections. The public health implications of the close proximity of the wild natural reservoir hosts of the human T. b. gambiense Dutton, 1902 parasites at the Kainji Wild Life park is discussed.

Flagellar Membrane Proteins of Tetraselmis striata Butcher (Chlorophyta)

Protist ◽  
2000 ◽  
Vol 151 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Stefan Gödel ◽  
Burkhard Becker ◽  
Michael Melkonian
Keyword(s):  
Membrane Proteins ◽  
Flagellar Membrane ◽  
Tetraselmis Striata
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