Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease
Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Nature communications - 8(2017), 1 vom: 30. Okt., Seite 678 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lüningschrör, Patrick [VerfasserIn] |
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| Links: |
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| Themen: |
EC 3.6.5.2 |
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| Anmerkungen: |
Date Completed 29.01.2018 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-017-00689-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM277524059 |
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| 100 | 1 | |a Lüningschrör, Patrick |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease | ||
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| 700 | 1 | |a Dombert, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Heimann, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Perez-Lara, Angel |e verfasserin |4 aut | |
| 700 | 1 | |a Slotta, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Thau-Habermann, Nadine |e verfasserin |4 aut | |
| 700 | 1 | |a R von Collenberg, Cora |e verfasserin |4 aut | |
| 700 | 1 | |a Karl, Franziska |e verfasserin |4 aut | |
| 700 | 1 | |a Damme, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Horowitz, Arie |e verfasserin |4 aut | |
| 700 | 1 | |a Maystadt, Isabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Füchtbauer, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Füchtbauer, Ernst-Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Jablonka, Sibylle |e verfasserin |4 aut | |
| 700 | 1 | |a Blum, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Üçeyler, Nurcan |e verfasserin |4 aut | |
| 700 | 1 | |a Petri, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Jahn, Reinhard |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Sendtner, Michael |e verfasserin |4 aut | |
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