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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. / 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; Sendtner, Michael.

In: Nature Communications, Vol. 8, No. 1, 678, 30.10.2017.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

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, Maystadt, I, Füchtbauer, A, Füchtbauer, EM, Jablonka, S, Blum, R, Üçeyler, N, Petri, S, Kaltschmidt, B, Jahn, R, Kaltschmidt, C & Sendtner, M 2017, 'Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease', Nature Communications, vol. 8, no. 1, 678. https://doi.org/10.1038/s41467-017-00689-z

APA

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., Füchtbauer, A., Füchtbauer, E. M., Jablonka, S., Blum, R., Üçeyler, N., Petri, S., Kaltschmidt, B., ... Sendtner, M. (2017). Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nature Communications, 8(1), [678]. https://doi.org/10.1038/s41467-017-00689-z

CBE

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, Maystadt I, Füchtbauer A, Füchtbauer EM, Jablonka S, Blum R, Üçeyler N, Petri S, Kaltschmidt B, Jahn R, Kaltschmidt C, Sendtner M. 2017. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nature Communications. 8(1):Article 678. https://doi.org/10.1038/s41467-017-00689-z

MLA

Vancouver

Lüningschrör P, Binotti B, Dombert B, Heimann P, Perez-Lara A, Slotta C et al. Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. Nature Communications. 2017 Oct 30;8(1). 678. https://doi.org/10.1038/s41467-017-00689-z

Author

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 ; Sendtner, Michael. / Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease. In: Nature Communications. 2017 ; Vol. 8, No. 1.

Bibtex

@article{c69effcf20814a3a9cccc991b1884f62,
title = "Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease",
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.",
author = "Patrick L{\"u}ningschr{\"o}r and Beyenech Binotti and Benjamin Dombert and Peter Heimann and Angel Perez-Lara and Carsten Slotta and Nadine Thau-Habermann and {Von Collenberg}, {Cora R.} and Franziska Karl and Markus Damme and Arie Horowitz and Isabelle Maystadt and Annette F{\"u}chtbauer and F{\"u}chtbauer, {Ernst Martin} and Sibylle Jablonka and Robert Blum and Nurcan {\"U}{\c c}eyler and Susanne Petri and Barbara Kaltschmidt and Reinhard Jahn and Christian Kaltschmidt and Michael Sendtner",
year = "2017",
month = oct,
day = "30",
doi = "10.1038/s41467-017-00689-z",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease

AU - Lüningschrör, Patrick

AU - Binotti, Beyenech

AU - Dombert, Benjamin

AU - Heimann, Peter

AU - Perez-Lara, Angel

AU - Slotta, Carsten

AU - Thau-Habermann, Nadine

AU - Von Collenberg, Cora R.

AU - Karl, Franziska

AU - Damme, Markus

AU - Horowitz, Arie

AU - Maystadt, Isabelle

AU - Füchtbauer, Annette

AU - Füchtbauer, Ernst Martin

AU - Jablonka, Sibylle

AU - Blum, Robert

AU - Üçeyler, Nurcan

AU - Petri, Susanne

AU - Kaltschmidt, Barbara

AU - Jahn, Reinhard

AU - Kaltschmidt, Christian

AU - Sendtner, Michael

PY - 2017/10/30

Y1 - 2017/10/30

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85032487264&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00689-z

DO - 10.1038/s41467-017-00689-z

M3 - Journal article

C2 - 29084947

AN - SCOPUS:85032487264

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 678

ER -