Rab32 family proteins and their interactors
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Abstract
The ER mitochondria-associated membrane (MAM) is a hub for many calcium-mediated processes required for cell survival, including apoptosis, autophagy, and ATP production. In this thesis, we identified and characterized the interaction between MAM-enriched Rab32 and its effector Drp1, a master regulator of mitochondrial fission. Evolutionary studies of Rab32 suggest that it forms a family with Rab38 and Rab29. While only Rab32 and Rab38 participate in melanosome trafficking, all family members interact with Drp1 to influence the mitochondria phenotype, Rab32 being the stronger interactor, followed by Rab38 and Rab29. Moreover, I was also able to determine that Rab32 interacts with syntaxin-17, a MAM-enriched SNARE protein which, like Rab32, participates in autophagy; Rab29 showed a weaker interaction with this SNARE, while this interaction was not seen with Rab38. Lastly, phylogenetic studies indicate that Rab29 and Rab38 are both a result of Holozoan expansion of Rab32, and that Rab29 diverged earlier in evolution from Rab32 than Rab38.