Trypanosome TOR complex 2 functions in cytokinesis

Antonio Barquilla1, Miguel Navarro

  • 1Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, CSIC, (Spanish National Research Council), Avda. del Conocimiento s/n, Granada, Spain.

Insights

Target of rapamycin (TOR) proteins regulate cell growth in eukaryotes. In Trypanosoma brucei, TbTOR1 controls cell cycle and protein synthesis, while TbTOR2 is crucial for cell polarization, endocytosis, and cytokinesis.

Area of Science:

  • Cell Biology
  • Parasitology
  • Molecular Biology

Background:

  • The target of rapamycin (TOR) pathway is a critical regulator of cell growth, metabolism, and survival in eukaryotes.
  • Understanding TOR function in diverse organisms like Trypanosoma brucei provides insights into conserved and divergent cellular processes.

Purpose of the Study:

  • To identify and characterize TOR orthologs in Trypanosoma brucei.
  • To investigate the specific roles of TbTOR1 and TbTOR2 in trypanosome cell biology.
  • To explore the mechanism of rapamycin action in T. brucei.

Main Methods:

  • Identification and characterization of TOR orthologs in T. brucei.
  • Depletion studies to assess the function of TbTOR1 and TbTOR2.
  • Analysis of rapamycin's effect on T. brucei cell growth and TOR complex formation.

Main Results:

  • Two functional TOR orthologs (TbTOR1, TbTOR2) and two related proteins were identified in T. brucei.
  • TbTOR1 depletion caused G1 arrest and inhibited protein synthesis.
  • TbTOR2 depletion resulted in defects in cell polarization, endocytosis, and cytokinesis.
  • Rapamycin inhibited T. brucei growth by preventing TORC2 complex formation, uniquely affecting TORC2 but not TORC1.

Conclusions:

  • TbTOR1 and TbTOR2 play distinct and essential roles in regulating cell growth, protein synthesis, and cytokinesis in T. brucei.
  • T. brucei exhibits unique TOR signaling, with rapamycin specifically inhibiting TORC2.
  • TOR proteins are key regulators of cell growth and cytokinesis in T. brucei, potentially influencing developmental differentiation.

Related Concept Videos

Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Spindle Assembly02:50

Spindle Assembly

Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
The Contractile Ring02:15

The Contractile Ring

Contractile rings are composed of microfilaments and are responsible for separating the daughter cells during cytokinesis. Contractile ring assembly proceeds along with other cell cycle events; however, very few mechanistic details are known about the timing and coordination of the contractile rings with the cell cycle.
A small GTPase, RhoA, controls the function and assembly of the contractile ring. RhoA belongs to the Ras superfamily of proteins. The activation of formins by RhoA promotes...
The Mitotic Spindle02:27

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...
The Mitotic Spindle02:27

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures bipolar mitotic...
Mitosis And Cytokinesis01:35

Mitosis And Cytokinesis

In eukaryotes, the cell division cycle is divided into distinct, coordinated cellular processes that include cell growth, DNA replication/chromosome duplication, chromosome distribution to daughter cells, and finally, cell division. The cell cycle is tightly regulated by its regulatory systems as well as extracellular signals that affect cell proliferation.
The processes of the cell cycle occur over approximately 24 hours (in typical human cells) and in two major distinguishable stages. The...