The Actomyosin System is Essential for Maintaining the Complex Endosomal Architecture in Bloodstream Form Trypanosoma brucei

المفاهيم الأساسية

The actomyosin system, consisting of actin and the class I myosin TbMyo1, is essential for maintaining the complex three-dimensional architecture of the endosomal system in bloodstream form Trypanosoma brucei.

الملخص

The study investigates the role of the actomyosin system in the bloodstream form of the parasitic protist Trypanosoma brucei. The actomyosin system in T. brucei is highly simplified, consisting of only one actin gene and two myosin genes.
Key findings:

TbMyo1, the class I myosin, has a large cytosolic pool and can translocate actin filaments in vitro at a relatively high velocity of 130 nm/s.
TbMyo1 localizes to the endosomal system, colocalizing with markers of early and late endosomes, but not recycling endosomes. It is also found associated with glycosomes.
Simultaneous visualization of actin and TbMyo1 using an anti-actin chromobody shows extensive overlap between the two, suggesting a tight association between the actomyosin system and the endosomal network.
Disruption of the actomyosin system using the actin-depolymerizing drug latrunculin A leads to a specific loss of endosomal structure and integrity, while leaving the Golgi and clathrin-mediated endocytosis at the flagellar pocket unaffected.
These results indicate that the actomyosin system is essential for maintaining the complex three-dimensional architecture of the endosomal system in bloodstream form T. brucei, likely playing a role in post-endocytic trafficking events within this interconnected membrane network.

الإحصائيات

The mean velocity of TbMyo1-mediated actin filament translocation was 130 ± 40 nm/s.
Quantification of the biochemical fractionation data showed that around 40% of TbMyo1 was in the cytosolic fraction and 40% was in the cytoskeleton-associated fraction.
Correlation analysis showed that TbMyo1 had a weak correlation with endocytic cargo markers BSA (ρ = 0.17) and transferrin (ρ = 0.20), but a stronger correlation with the actin chromobody signal (ρ = 0.63).

اقتباسات

"The actomyosin system is required for maintaining endosomal integrity in T. brucei."
"Disruption of the actomyosin system using the actin-depolymerising drug latrunculin A resulted in a delocalisation of both the actin chromobody signal and an endosomal marker, and was accompanied by a specific loss of endosomal structure."

الرؤى الأساسية المستخلصة من

The actomyosin system is essential for the integrity of the endosomal system in bloodstream form Trypanosoma brucei

by Link,F., Jun... في www.biorxiv.org 01-31-2024

https://www.biorxiv.org/content/10.1101/2024.01.29.577824v1

استفسارات أعمق

How might the actomyosin system be involved in the trafficking and organization of glycosomes in T. brucei?

The actomyosin system in T. brucei, particularly the class I myosin TbMyo1, plays a crucial role in the trafficking and organization of glycosomes. Glycosomes are specialized organelles in trypanosomes that compartmentalize glycolytic enzymes. The association of TbMyo1 with glycosomes, as observed in the study, suggests that it may be involved in the dynamic regulation of glycosome positioning and function.
One possible mechanism by which the actomyosin system contributes to glycosome trafficking is through motor-driven movement along actin filaments. TbMyo1, being a myosin motor protein, can translocate actin filaments at a relatively high speed. This motor activity could facilitate the movement of glycosomes to specific locations within the cell, ensuring their proper distribution and function. Additionally, the interaction between TbMyo1 and glycosomes may be essential for maintaining the structural integrity of these organelles, potentially influencing their biogenesis and turnover.
Furthermore, the actomyosin system could be involved in coordinating the positioning of glycosomes in response to cellular cues or environmental changes. By interacting with actin filaments and potentially other cytoskeletal components, TbMyo1 may contribute to the spatial organization of glycosomes in the cell, ensuring efficient metabolic processes and adaptation to varying conditions. Overall, the actomyosin system likely plays a multifaceted role in glycosome trafficking and organization in T. brucei, contributing to the proper functioning of these essential organelles.

How might the actomyosin system be involved in the trafficking and organization of glycosomes in T. brucei?

The actomyosin system in T. brucei is crucial for maintaining the complex architecture of the endosomal network through several potential mechanisms. Firstly, the motor activity of TbMyo1, a class I myosin, enables the active translocation of actin filaments, which could facilitate the movement and organization of endosomal membranes. By interacting with actin filaments, TbMyo1 may generate the force necessary for membrane remodeling, vesicle transport, and the maintenance of membrane curvature within the endosomal network.
Secondly, the association of TbMyo1 with specific endosomal markers, such as TbRab5A and TbRab7, suggests that it plays a role in regulating endosomal trafficking and maturation. TbMyo1 may be involved in the transport of endocytic cargo, the fusion of endosomal compartments, and the dynamic rearrangement of membrane structures within the network. This coordination of membrane dynamics by the actomyosin system could contribute to the stability and functionality of the endosomal system in T. brucei.
Moreover, the actomyosin system may participate in the spatial organization of endosomal subdomains and the maintenance of membrane morphology. By interacting with membrane-bound proteins and lipids, TbMyo1 could help anchor endosomal membranes to the cytoskeleton, regulate membrane tension, and facilitate membrane fusion events. This structural support provided by the actomyosin system could be essential for the maintenance of the interconnected and continuous nature of the endosomal network in trypanosomes.
In summary, the actomyosin system likely contributes to the trafficking and organization of the endosomal network in T. brucei by mediating membrane dynamics, cargo transport, and structural integrity within the complex network of interconnected membranes.

Could the insights gained from this study on the role of the actomyosin system in T. brucei endosomal integrity be applicable to other eukaryotic cell types with complex endomembrane systems?

The insights gained from the study on the role of the actomyosin system in T. brucei endosomal integrity could have broader implications for other eukaryotic cell types with complex endomembrane systems. The actomyosin system is a fundamental component of the cytoskeleton in many eukaryotic cells, and its involvement in membrane dynamics and organelle organization is conserved across diverse organisms. Therefore, the following points highlight how the findings from this study could be applicable to other cell types:

Membrane Trafficking: The actomyosin system's role in mediating membrane trafficking and cargo transport within the endosomal network of T. brucei is a fundamental process in many eukaryotic cells. The motor activity of myosin proteins, such as TbMyo1, is essential for vesicle movement, organelle positioning, and membrane fusion events. Similar mechanisms involving actomyosin interactions with endosomal membranes and cytoskeletal components likely exist in other cell types with complex endomembrane systems.

Endosomal Organization: The actomyosin system's contribution to the organization and maintenance of the endosomal network in T. brucei underscores its importance in regulating membrane morphology and subcellular compartmentalization. This aspect of actomyosin function is likely conserved in other eukaryotic cells with intricate endomembrane systems, where the cytoskeleton plays a critical role in shaping organelle architecture and ensuring proper cellular function.

Glycosome Dynamics: The association of TbMyo1 with glycosomes in T. brucei highlights the potential involvement of the actomyosin system in regulating organelle dynamics and positioning. Glycosomes are specialized organelles found in various eukaryotic cells, and the actomyosin system may play a similar role in coordinating glycosome trafficking and organization in other cell types.

Overall, the fundamental cellular processes governed by the actomyosin system in T. brucei, such as membrane trafficking, organelle organization, and cytoskeletal interactions, are likely to be relevant to a wide range of eukaryotic cell types with complex endomembrane systems. The insights from this study provide a foundation for understanding the universal principles of actomyosin function in cellular dynamics and organelle homeostasis.