Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector

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作者
Amrita Rai
Anurag K. Singh
Nathalie Bleimling
Guido Posern
Ingrid R. Vetter
Roger S. Goody
机构
[1] Max Planck Institute of Molecular Physiology,Department of Structural Biochemistry
[2] Martin Luther University Halle-Wittenberg,Institute for Physiological Chemistry
[3] Max Planck Institute of Molecular Physiology,Department of Mechanistic Cell Biology
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Nature Communications | / 13卷
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摘要
In their GTP-bound (active) form, Rab proteins interact with effector proteins that control downstream signaling. One such Rab15 effector is Rep15, which is known to have a role in receptor recycling from the endocytic recycling compartment but otherwise remains poorly characterized. Here, we report the characterization of the Rep15:Rab15 interaction and identification of Rab3 paralogs and Rab34 as Rep15 interacting partners from a yeast two-hybrid assay. Biochemical validation of the interactions is presented and crystal structures of the Rep15:Rab3B and Rep15:Rab3C complexes provide additional mechanistic insight. We find that Rep15 adopts a globular structure that is distinct from other reported Rab15, Rab3 and Rab34 effectors. Structure-based mutagenesis experiments explain the Rep15:Rab interaction specificity. Rep15 depletion in U138MG glioblastoma cells impairs cell proliferation, cell migration and receptor recycling, underscoring the need for further clarification of the role of Rep15 in cancer.
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