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Updated: May 13, 2026
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Evolution of Tre-2/Bub2/Cdc16 (TBC) Rab GTPase-activating proteins
Carme Gabernet-Castello1, Amanda J O'Reilly, Joel B Dacks
1Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
Molecular Biology of the Cell
|March 15, 2013
Summary
This study reveals the ancient evolutionary history of TBC proteins, key regulators of Rab GTPases. Findings highlight conserved TBC domain architecture and coevolution with Rabs, shaping intracellular trafficking.
Area of Science:
- Molecular Biology
- Cell Biology
- Evolutionary Biology
Background:
- Rab GTPases are crucial regulators of intracellular trafficking and compartment organization.
- GTPase-activating proteins (GAPs) modulate Rab activity; many GAPs contain a Tre-2/Bub2/Cdc16 (TBC) domain.
- The evolutionary history and characterization of the TBC protein family remain largely unexplored.
Purpose of the Study:
- To reconstruct the evolutionary history of the TBC protein family across eukaryotes.
- To investigate the conservation and evolution of TBC-domain architecture and its relationship with Rab GTPases.
- To understand the role of TBC proteins in shaping the endomembrane system.
Main Methods:
- Phylogenetic analysis of pan-eukaryotic datasets using the ScrollSaw method.
- Reconstruction of the evolutionary history of the TBC protein family.
- Comparative analysis of TBC and Rab complements across genomes.
Main Results:
- Identified a sophisticated and ancient TBC protein complement with at least 10 members.
- Demonstrated that the TBC complement is generally smaller than the Rab cohort, suggesting Rab/TBC coevolution.
- Observed conserved TBC-domain architecture in modern eukaryotes, alongside evidence of ancestral subfamily conservation, new TBC evolution, and secondary losses.
Conclusions:
- The TBC protein family has a deep evolutionary history and complex structure.
- Rab and TBC proteins have coevolved, influencing intracellular trafficking pathways.
- Evolutionary dynamics of TBC proteins provide insights into the development of the eukaryotic endomembrane system.
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