RabGEFs are a major determinant for specific Rab membrane targeting

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Abstract

Eukaryotic cells critically depend on the correct regulation of intracellular vesicular trafficking to transport biological material. The Rab subfamily of small guanosine triphosphatases controls these processes by acting as a molecular on/off switch. To fulfill their function, active Rabproteins need to localize to intracellular membranes via posttranslationally attached geranylgeranyl lipids. Each member of the manifold Rab family localizes specifically to a distinct membrane, but it is unclear how this specific membrane recruitment is achieved. Here, we demonstrate that Rab-activating guanosine diphosphate/guanosine triphosphate exchange factors (GEFs) display the minimal targeting machinery for recruiting Rabs from the cytos to the correct membrane using the Rab-GEF pairs Rab5A-Rabex-5, Rab1A-DrrA, and Rab8-Rabin8 as model systems. Specific mistargeting of Rabex-5/DrrA/Rabin8 to mitochondria led to catalytic recruitment of Rab5A/ Rab1A/Rab8A in atime-dependent manner that required the catalytic activity of the GEF. Therefore, RabGEFs are major determinants for specific Rab membrane targeting. © 2013 Blümer et al.

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Blümer, J., Rey, J., Dehmelt, L., Maze, T., Wu, Y. W., Bastiaens, P., … Itzen, A. (2013). RabGEFs are a major determinant for specific Rab membrane targeting. Journal of Cell Biology, 200(3), 287–300. https://doi.org/10.1083/jcb.201209113

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