Document Type
Article
Publication Date
12-1-2017
Abstract
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.
Recommended Citation
Lüningschrör, Patrick; Binotti, Beyenech; Dombert, Benjamin; Heimann, Peter; Perez-Lara, Angel; Slotta, Carsten; Thau-Habermann, Nadine; von Collenberg, Cora R.; Karl, Franziska; Damme, Markus; Horowitz, Arie; Maystadt, Isabelle; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; Jablonka, Sibylle; Blum, Robert; Üçeyler, Nurcan; Petri, Susanne; Kaltschmidt, Barbara; Jahn, Reinhard; Kaltschmidt, Christian; and Sendtner, Michael, "Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease." (2017). Department of Medicine Faculty Papers. Paper 220.
https://jdc.jefferson.edu/medfp/220
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
29084947
Comments
This article has been peer reviewed. It is the author’s final published version in Nature Communications
Volume 8, Issue 1, December 2017, Article number 678.
The published version is available at DOI: 10.1038/s41467-017-00689-z. Copyright © Lüningschrör et al.