title: The GTPase Rab26 links synaptic vesicles to the autophagy pathway.
abstract: 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.
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Beyenech
authors: B
authors: Binotti
authors: School of Surgery, University of Western Australia, Crawley, Australia.
authors: Nathan J
authors: NJ
authors: Pavlos
authors: Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Dietmar
authors: D
authors: Riedel
authors: Facility for Transmission Electron Microscopy, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Dirk
authors: D
authors: Wenzel
authors: Research Group Molecular Cell Dynamics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Gerd
authors: G
authors: Vorbrüggen
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Amanda M
authors: AM
authors: Schalk
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Karin
authors: K
authors: Kühnel
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Janina
authors: J
authors: Boyken
authors: Synaptic Systems GmbH, Göttingen, Germany.
authors: Christian
authors: C
authors: Erck
authors: Synaptic Systems GmbH, Göttingen, Germany.
authors: Henrik
authors: H
authors: Martens
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: John J E
authors: JJ
authors: Chua
authors: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Reinhard
authors: R
authors: Jahn
mesh_terms: D000818:Animals; D001343:Autophagy; D066146:Cell Body / Q000378:metabolism; D002451:Cell Compartmentation; D002478:Cells, Cultured; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010588:Phagosomes / Q000378:metabolism; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D050505:Mutant Proteins; D033921:Vesicular Transport Proteins; C485184:enhanced green fluorescent protein; D006153:Guanosine Diphosphate; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; C577013:Atg16L1 protein, rat; C092137:Rab26 protein, rat; C578286:Rab26 protein, human; D020691:rab GTP-Binding Proteins
keywords: D. melanogaster; autophagy; human; neuroscience; rab proteins; rat; synaptic vesicles
references: J Cell Biol. 1973 May;57(2):551-65
references: 4121290
references: Neuron. 2012 Apr 26;74(2):277-84
references: 22542182
references: Methods Mol Biol. 2008;420:239-51
references: 18641951
references: J Cell Biol. 1973 May;57(2):499-524
references: 4348791
references: Neuron. 2004 Jul 22;43(2):221-36
references: 15260958
references: Neuron. 1993 Aug;11(2):253-66
references: 8394720
references: Nature. 2009 Mar 26;458(7237):445-52
references: 19325624
references: J Cell Biol. 1983 May;96(5):1374-88
references: 6404912
references: J Biol Chem. 2012 Dec 14;287(51):42784-94
references: 23105096
references: Acta Crystallogr D Biol Crystallogr. 2007 Jul;63(Pt 7):769-79
references: 17582168
references: Dev Cell. 2009 Sep;17(3):403-16
references: 19758564
references: Mol Biol Cell. 2008 Jul;19(7):2916-25
references: 18448665
references: Prog Neurobiol. 2011 Mar;93(3):313-40
references: 21216273
references: Small GTPases. 2011 Mar;2(2):77-81
references: 21776405
references: Annu Rev Cell Dev Biol. 2010;26:179-210
references: 20604708
references: Annu Rev Neurosci. 2012;35:369-89
references: 22715882
references: Nat Neurosci. 2001 Sep;4(9):908-16
references: 11528422
references: J Cell Biol. 1973 May;57(2):315-44
references: 4348786
references: Neuron. 2001 Dec 20;32(6):1013-26
references: 11754834
references: J Neurosci. 2010 Oct 6;30(40):13441-53
references: 20926670
references: Neuron. 2010 Nov 18;68(4):610-38
references: 21092854
references: Bioessays. 2008 Nov;30(11-12):1075-83
references: 18937340
references: J Neurosci. 1995 Jun;15(6):4328-42
references: 7540672
references: Curr Opin Neurobiol. 2013 Dec;23(6):990-6
references: 23871216
references: Nat Struct Mol Biol. 2014 Apr;21(4):336-45
references: 24699082
references: Nat Rev Mol Cell Biol. 2009 Aug;10(8):513-25
references: 19603039
references: Nat Methods. 2005 Dec;2(12):905-9
references: 16299475
references: Protein Expr Purif. 2005 May;41(1):207-34
references: 15915565
references: J Biol Chem. 1990 Aug 5;265(22):13007-15
references: 2115887
references: J Biol Chem. 2004 Mar 19;279(12):11480-8
references: 14699104
references: Curr Biol. 2011 Oct 25;21(20):1704-15
references: 22000105
references: J Neurosci. 2011 May 25;31(21):7817-30
references: 21613495
references: Histochem J. 1980 Jul;12(4):381-403
references: 7440248
references: Neuron. 2006 Mar 16;49(6):833-44
references: 16543132
references: Nat Neurosci. 2005 Jul;8(7):898-905
references: 16136672
references: Science. 1972 Jun 23;176(4041):1353-5
references: 5034553
references: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5862-7
references: 22451907
references: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11821-7
references: 16882731
references: J Neurosci Methods. 1997 Sep 5;76(1):1-5
references: 9334932
references: Nat Rev Neurosci. 2012 Jul;13(7):478-90
references: 22714019
references: J Biol Chem. 2000 Mar 31;275(13):9433-40
references: 10734089
references: Autophagy. 2011 Dec;7(12):1500-13
references: 22082872
references: Biophys J. 2010 Jul 21;99(2):675-84
references: 20643088
references: Neuron. 2013 Oct 30;80(3):648-57
references: 24183017
references: J Cell Sci. 2014 Mar 1;127(Pt 5):1018-32
references: 24413166
references: J Cell Sci. 2003 May 1;116(Pt 9):1679-88
references: 12665549
references: Cold Spring Harb Perspect Biol. 2012 Sep;4(9):a005645
references: 22763746
references: Mol Biol Cell. 2012 Aug;23(16):3193-202
references: 22740627
references: Cell. 1993 Jun 18;73(6):1091-9
references: 8513495
references: Autophagy. 2014 Mar;10(3):397-407
references: 24419294
references: Nat Rev Mol Cell Biol. 2013 Dec;14(12):759-74
references: 24201109
references: J Neurogenet. 1990 Nov;7(1):15-29
references: 2129171
references: Arch Oral Biol. 2006 Feb;51(2):89-95
references: 16076461
references: Nat Chem Biol. 2010 Jul;6(7):534-40
references: 20512138
references: Curr Biol. 2003 Dec 2;13(23):2073-81
references: 14653997
references: Science. 2008 Feb 29;319(5867):1253-6
references: 18258863
references: Pharmacol Rev. 2007 Mar;59(1):14-39
references: 17329546
references: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5600-5
references: 15809437
references: Science. 1971 Aug 20;173(3998):733-6
references: 4327989
references: Nature. 2006 Apr 13;440(7086):935-9
references: 16612384
references: Autophagy. 2012 Apr;8(4):445-544
references: 22966490
references: Curr Opin Neurobiol. 2012 Jun;22(3):438-45
references: 22036016
references: J Biol Chem. 1993 Aug 25;268(24):18143-50
references: 8349690
references: Annu Rev Cell Dev Biol. 2011;27:107-32
references: 21801009
references: J Neurosci. 2010 Dec 8;30(49):16718-29
references: 21148011
references: FEBS Lett. 2004 Jun 18;568(1-3):23-9
references: 15196914
references: J Proteome Res. 2012 Sep 7;11(9):4722-32
references: 22871113
references: Cell Mol Life Sci. 2008 Sep;65(18):2801-13
references: 18726178
references: J Cell Biol. 2012 Feb 20;196(4):407-17
references: 22331844
references: Cell. 2006 Nov 17;127(4):831-46
references: 17110340
references: Genetics. 2007 Jun;176(2):1307-22
references: 17409086
references: J Neurosci. 1982 Mar;2(3):284-91
references: 7062109
references: Mol Cell Biol. 2010 Mar;30(5):1269-84
references: 20038531
references: J Mol Biol. 2001 Nov 2;313(4):889-901
references: 11697911
references: J Neurosci. 2010 Feb 3;30(5):1798-809
references: 20130189
references: Proc Natl Acad Sci U S A. 1985 Jun;82(12):4137-41
references: 3923488
references: Development. 2003 Aug;130(16):3671-82
references: 12835384
references: Neuron. 2006 Jul 20;51(2):179-86
references: 16846853
references: Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905
references: 12461556
references: Nat Rev Neurosci. 2013 May;14(5):311-21
references: 23595014
references: Cell Mol Life Sci. 2011 Oct;68(20):3349-58
references: 21687989
references: J Neurosci. 2000 Jul 1;20(13):4904-11
references: 10864948
references: Cell. 2007 Sep 7;130(5):943-57
references: 17803915
references: Nat Cell Biol. 2010 Aug;12(8):747-57
references: 20639872
references: Nature. 2001 Jul 26;412(6845):449-52
references: 11473321
references: Neuron. 1989 Dec;3(6):715-20
references: 2577130
references: Cell Mol Life Sci. 2005 Aug;62(15):1657-70
references: 15924270
references: Nat Neurosci. 2006 Mar;9(3):315-21
references: 16462738