Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease

Lüningschrör P, Binotti B, Dombert B, Heimann P, Perez-Lara A, Slotta C, Thau-Habermann N, von Collenberg CR, Karl F, Damme M, Horowitz A, et al. (2017)
NATURE COMMUNICATIONS 8: 678.

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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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Lüningschrör P, Binotti B, Dombert B, et al. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS. 2017;8: 678.
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., et al. (2017). Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS, 8, 678. doi:10.1038/s41467-017-00689-z
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C. R., Karl, F., Damme, M., et al. (2017). Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS 8:678.
Lüningschrör, P., et al., 2017. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS, 8: 678.
P. Lüningschrör, et al., “Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease”, NATURE COMMUNICATIONS, vol. 8, 2017, : 678.
Lüningschrör, P., Binotti, B., Dombert, B., Heimann, P., Perez-Lara, A., Slotta, C., Thau-Habermann, N., von Collenberg, C.R., Karl, F., Damme, M., Horowitz, A., Maystadt, I., Fuechtbauer, A., Fuechtbauer, E.-M., Jablonka, S., Blum, R., Ueceyler, N., Petri, S., Kaltschmidt, B., Jahn, R., Kaltschmidt, C., Sendtner, M.: Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. NATURE COMMUNICATIONS. 8, : 678 (2017).
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, Fuechtbauer, Annette, Fuechtbauer, Ernst-Martin, Jablonka, Sibylle, Blum, Robert, Ueceyler, 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”. NATURE COMMUNICATIONS 8 (2017): 678.
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