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bioRxiv · 10.1101/2024.11.27.625582

Rab2B promotes chaperonin-mediated actin folding and prevents developmental transcription reprogramming and quiescence in trypanosomes

Li, F.-J.·Dong, X.·Huang, Y.·Hu, D.·Chae, E.·He, C. Y.
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Abstract

The Rab family of small GTPases are regulators of intracellular membrane trafficking. Rab2B, a Golgi-resident Rab GTPase, has been shown to function in ER-Golgi transport and autophagosome-lysosome fusion in mammalian cells and Drosophila. In Trypanosoma brucei, the autophagy-related function of Rab2B was conserved and depletion of Rab2B blocked autophagosome-lysosome fusion. Intriguingly, depletion of Rab2B induced differentiation of T. brucei from a proliferative slender form to a quiescent stumpy form, a step crucial for parasite transmission. Chaperonin CCT/TRiC was identified as an effector of Rab2B. Depletion of CCT/TRiC subunits or actin (a known CCT/TRiC substrate), or blocking actin polymerisation with Latrunculin A all triggered differentiation, suggesting a role of Rab2B on CCT/TRiC-mediated actin folding. Using an actin chromobody, we identified a pool of nuclear actin that is crucial for transcription reprogramming and life cycle differentiation in T. brucei. The study revealed a function of Rab2B and actin in T. brucei transcription reprogramming leading to cell differentiation, and an unexpected role of Rab2B and CCT/TRiC mediated actin folding.

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Li, F.-J., Dong, X., Huang, Y., Hu, D., Chae, E., He, C. Y.. 2024-11-28. Rab2B promotes chaperonin-mediated actin folding and prevents developmental transcription reprogramming and quiescence in trypanosomes. https://doi.org/10.1101/2024.11.27.625582

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