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Bassoon Controls Presynaptic Autophagy through Atg5.

Neuron | 2017

Mechanisms regulating the surveillance and clearance of synaptic proteins are not well understood. Intriguingly, the loss of the presynaptic active zone proteins Piccolo and Bassoon triggers the loss of synaptic vesicles (SVs) and compromises synaptic integrity. Here we report that the destruction of SVs in boutons lacking Piccolo and Bassoon was associated with the induction of presynaptic autophagy, a process that depended on poly-ubiquitination, but not the E3 ubiquitin ligase Siah1. Surprisingly, gain or loss of function (LOF) of Bassoon alone suppressed or enhanced presynaptic autophagy, respectively, implying a fundamental role for Bassoon in the local regulation of presynaptic autophagy. Mechanistically, Bassoon was found to interact with Atg5, an E3-like ligase essential for autophagy, and to inhibit the induction of autophagy in heterologous cells. Importantly, Atg5 LOF as well as targeting an Atg5-binding peptide derived from Bassoon inhibited presynaptic autophagy in boutons lacking Piccolo and Bassoon, providing insights into the molecular mechanisms regulating presynaptic autophagy.

Pubmed ID: 28231469 RIS Download

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Antibodies used in this publication

Associated grants

  • Agency: BLRD VA, United States
    Id: I21 BX003357

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This is a list of tools and resources that we have found mentioned in this publication.


Anti-Atg5 Antibody (antibody)

RRID:AB_2688028

This polyclonal targets Atg5

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anti-LC3 (antibody)

RRID:AB_10897859

This monoclonal targets anti-LC3

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LC3 Polyclonal Antibody (antibody)

RRID:AB_843283

This polyclonal targets LC3

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Anti-Bassoon (antibody)

RRID:AB_2619827

This monoclonal targets Bassoon

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Anti-Bassoon (antibody)

RRID:AB_2290619

This polyclonal targets Bassoon

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Atg16L Polyclonal Antibody (antibody)

RRID:AB_1278757

This polyclonal targets Human Atg16L1

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Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (antibody)

RRID:AB_2533967

This polyclonal secondary targets IgG (H+L)

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Anti-VGLUT 1 (antibody)

RRID:AB_887877

This polyclonal targets VGLUT 1

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Anti-Synaptophysin 1 (antibody)

RRID:AB_887905

This polyclonal targets Synaptophysin 1

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Anti-Synaptophysin 1 (antibody)

RRID:AB_887824

This monoclonal targets Synaptophysin 1

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p62 Lck Ligand (antibody)

RRID:AB_398152

This monoclonal targets p62 Lck Ligand

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RFP Antibody Pre-adsorbed (antibody)

RRID:AB_2209751

This polyclonal targets RFP

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Anti-Homer 1 (antibody)

RRID:AB_887730

This polyclonal targets Homer 1

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Anti-GFP (antibody)

RRID:AB_390913

This monoclonal targets GFP

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ATG5 Antibody (antibody)

RRID:AB_828587

This unknown targets ATG5

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Anti-Ankyrin-G (Staining) Antibody (antibody)

RRID:AB_10673030

This monoclonal targets Ankyrin-G (Staining)

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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HeLa (cell line)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

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HEK293T (cell line)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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COS-7 (cell line)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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