RabGEFs are a major determinant for specific Rab membrane targeting |
| |
Authors: | Julia Blümer Juliana Rey Leif Dehmelt Tomá? Mazel Yao-Wen Wu Philippe Bastiaens Roger S. Goody Aymelt Itzen |
| |
Affiliation: | 1.Department of Physical Biochemistry, and 2.Department of Systemic Cell Biology, Max-Planck-Institute of Molecular Physiology, 44227 Dortmund, Germany;3.Chemistry Department, Center for Integrated Protein Science Munich, Technische Universität München, 85747 Garching, Germany;4.Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, 44227 Dortmund, Germany |
| |
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 Rab proteins 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 cytosol 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 a time-dependent manner that required the catalytic activity of the GEF. Therefore, RabGEFs are major determinants for specific Rab membrane targeting. |
| |
Keywords: | |
|
|