School of Surgery, University of Western Australia, Crawley, Australia
Dietmar Riedel
Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Dirk Wenzel
Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Gerd Vorbrüggen
Research Group Molecular Cell Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany; Department of Developmental Biology, Georg-August-University Göttingen, Göttingen, Germany
Amanda M Schalk
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Karin Kühnel
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Janina Boyken
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy. Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites. Overexpression of active but not of GDP-preferring Rab26 enhances vesicle clustering, which is particularly conspicuous for the EGFP-tagged variant, resulting in a massive accumulation of synaptic vesicles in neuronal somata without altering the distribution of other organelles. Both endogenous and induced clusters co-localize with autophagy-related proteins such as Atg16L1, LC3B and Rab33B but not with other organelles. Furthermore, Atg16L1 appears to be a direct effector of Rab26 and binds Rab26 in its GTP-bound form, albeit only with low affinity. We propose that Rab26 selectively directs synaptic and secretory vesicles into preautophagosomal structures, suggesting the presence of a novel pathway for degradation of synaptic vesicles.
