TY  - JOUR
A1  - Lüningschrör, Patrick
A1  - Binotti, Beyenech
A1  - Dombert, Benjamin
A1  - Heimann, Peter
A1  - Perez-Lara, Angel
A1  - Slotta, Carsten
A1  - Thau-Habermann, Nadine
A1  - von Collenberg, Cora R.
A1  - Karl, Franziska
A1  - Damme, Markus
A1  - Horowitz, Arie
A1  - Maystadt, Isabelle
A1  - Füchtbauer, Annette
A1  - Füchtbauer, Ernst-Martin
A1  - Jablonka, Sibylle
A1  - Blum, Robert
A1  - Üçeyler, Nurcan
A1  - Petri, Susanne
A1  - Kaltschmidt, Barbara
A1  - Jahn, Reinhard
A1  - Kaltschmidt, Christian
A1  - Sendtner, Michael
T1  - Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease
JF  - Nature Communications
N2  - 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.
KW  - autophagy
KW  - synaptic vesicles
KW  - Pleckstrin homology containing family member 5 (Plekhg5)
KW  - regulation
KW  - motoneuron disease
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170048
VL  - 8
IS  - 678
ER  -