TbVps15 is required for vesicular transport and cytokinesis in Trypanosoma brucei. 2018

Alejandra C Schoijet, and Kildare Miranda, and Tamara Sternlieb, and Nadia M Barrera, and Wendell Girard-Dias, and Wanderley de Souza, and Guillermo D Alonso
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina; Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina.

The class III phosphatidylinositol 3-kinase (PI3K) Vps34 is an important regulator of key cellular functions, including cell growth, survival, intracellular trafficking, autophagy and nutrient sensing. In yeast, Vps34 is associated with the putative serine/threonine protein kinase Vps15, however, its role in signaling has not been deeply evaluated. Here, we have identified the Vps15 orthologue in Trypanosoma brucei, named TbVps15. Knockdown of TbVps15 expression by interference RNA resulted in inhibition of cell growth and blockage of cytokinesis. Scanning electron microcopy revealed a variety of morphological abnormalities, with enlarged parasites and dividing cells that often exhibited a detached flagellum. Transmission electron microscopy analysis of TbVps15 RNAi cells showed an increase in intracellular vacuoles of the endomembrane system and some cells displayed an enlargement of the flagellar pocket, a common feature of cells defective in endocytosis. Moreover, uptake of dextran, transferrin and Concanavalin A was impaired. Finally, TbVps15 downregulation affected the PI3K activity, supporting the hypothesis that TbVps15 and TbVps34 form a complex as occurs in other organisms. In summary, we propose that TbVps15 has a role in the maintenance of cytokinesis, endocytosis and intracellular trafficking in T. brucei.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D014346 Trypanosoma brucei brucei A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina). Trypanosoma brucei,Trypanosoma brucei bruceus,Trypanosoma bruceus,brucei brucei, Trypanosoma,brucei, Trypanosoma brucei,bruceus, Trypanosoma,bruceus, Trypanosoma brucei
D046529 Microscopy, Electron, Transmission Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen. Electron Diffraction Microscopy,Electron Microscopy, Transmission,Microscopy, Electron Diffraction,Transmission Electron Microscopy,Diffraction Microscopy, Electron,Microscopy, Transmission Electron
D048749 Cytokinesis The process by which the CYTOPLASM of a cell is divided. Cytoplasmic Division,Cytokineses,Cytoplasmic Divisions,Division, Cytoplasmic,Divisions, Cytoplasmic
D055785 Gene Knockdown Techniques The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES. Gene Knock Down Techniques,Gene Knock Down,Gene Knock-Down,Gene Knock-Down Techniques,Gene Knockdown,Gene Knock Downs,Gene Knock-Down Technique,Gene Knock-Downs,Gene Knockdown Technique,Gene Knockdowns,Knock Down, Gene,Knock Downs, Gene,Knock-Down Technique, Gene,Knock-Down Techniques, Gene,Knock-Down, Gene,Knock-Downs, Gene,Knockdown Technique, Gene,Knockdown Techniques, Gene,Knockdown, Gene,Knockdowns, Gene,Technique, Gene Knock-Down,Technique, Gene Knockdown,Techniques, Gene Knock-Down,Techniques, Gene Knockdown
D058539 Phosphatidylinositol 3-Kinase A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate. 1-Phosphatidylinositol 3-Kinase,Phosphoinositide 3 Kinase,1 Phosphatidylinositol 3 Kinase,Kinase, Phosphoinositide 3,Phosphatidylinositol 3 Kinase
D058546 Class III Phosphatidylinositol 3-Kinases A phosphatidylinositol 3-kinase subclass that includes enzymes whose specificity is limited to 1-phosphatidylinositol. Members of this class play a role in vesicular transport and in the regulation of TOR KINASES. Phosphatidylinositol 3-Kinase, Class III,Class III Phosphatidylinositol 3-Kinase Catalytic Subunit,Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3,Phosphatidylinositol 3-Kinase p100 Subunit,VPS34 Sorting Protein,Vacuolar Protein Sorting 34 Protein,Vps34 Phosphatidylinositol 3-Kinase,Class III Phosphatidylinositol 3 Kinase Catalytic Subunit,Class III Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 Kinase Catalytic Subunit Type 3,Phosphatidylinositol 3 Kinase p100 Subunit,Phosphatidylinositol 3 Kinase, Class III,Phosphatidylinositol 3-Kinase, Vps34,Vps34 Phosphatidylinositol 3 Kinase
D058571 Vacuolar Sorting Protein VPS15 A 150 kDa protein serine-threonine kinase that is found as a regulatory subunit of the class III phosphatidylinositol 3-kinases. The protein is believed to play an important role in the regulation of vesicular trafficking with the cell. Class III Phosphatidylinositol 3-Kinase Regulatory Subunit,Class III Phosphatidylinositol 3-Kinase, p150 Subunit,Phosphatidylinositol 3-Kinase, Regulatory Subunit, Polypeptide 4, p150,Phosphoinositide-3-kinase, Regulatory Subunit 4,VPS15 Protein,Vacuolar Protein Sorting 15,Vps15 Protein Kinase,Class III Phosphatidylinositol 3 Kinase Regulatory Subunit,Class III Phosphatidylinositol 3 Kinase, p150 Subunit,Phosphoinositide 3 kinase, Regulatory Subunit 4,Protein Kinase, Vps15
D018562 Disease Transmission, Infectious The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal or vertical (INFECTIOUS DISEASE TRANSMISSION, VERTICAL). Close-Contact Infectious Disease Transmission,Close-Contact Transmission,Community Spread,Community Transmission,Disease Superspreader Event,Disease Superspreading,Droplet Transmission of Infectious Disease,Droplet Transmission, Infectious Disease,Infectious Disease Droplet Transmission,Person-to-Person Transmission,Autochthonous Transmission,Communicable Disease Transmission,Horizontal Transmission of Infection,Horizontal Transmission of Infectious Disease,Infection Transmission,Infection Transmission, Horizontal,Infectious Disease Transmission,Infectious Disease Transmission, Horizontal,Pathogen Transmission,Pathogen Transmission, Horizontal,Transmission of Infectious Disease,Transmission, Infectious Disease,Autochthonous Transmissions,Close Contact Infectious Disease Transmission,Close Contact Transmission,Close-Contact Transmissions,Community Transmissions,Disease Superspreader Events,Disease Superspreadings,Disease Transmission, Communicable,Event, Disease Superspreader,Events, Disease Superspreader,Infection Horizontal Transmission,Person to Person Transmission,Superspreader Event, Disease,Superspreader Events, Disease,Superspreading, Disease,Superspreadings, Disease,Transmission, Autochthonous,Transmission, Close-Contact,Transmission, Communicable Disease,Transmission, Infection,Transmission, Pathogen,Transmission, Person-to-Person,Transmissions, Autochthonous,Transmissions, Community

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