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(1): 678.
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Autor*in
Lüningschrör, PatrickUniBi;
Binotti, Beyenech;
Dombert, Benjamin;
Heimann, PeterUniBi;
Perez-Lara, Angel;
Slotta, CarstenUniBi;
Thau-Habermann, Nadine;
von Collenberg, Cora R.;
Karl, Franziska;
Damme, Markus;
Horowitz, Arie;
Maystadt, Isabelle
Alle
Alle
Einrichtung
Abstract / Bemerkung
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.
Erscheinungsjahr
2017
Zeitschriftentitel
NATURE COMMUNICATIONS
Band
8
Ausgabe
1
Art.-Nr.
678
Urheberrecht / Lizenzen
ISSN
2041-1723
Page URI
https://pub.uni-bielefeld.de/record/2915086
Zitieren
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(1): 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(1), 678. doi:10.1038/s41467-017-00689-z
Lüningschrör, Patrick, Binotti, Beyenech, Dombert, Benjamin, Heimann, Peter, Perez-Lara, Angel, Slotta, Carsten, Thau-Habermann, Nadine, et al. 2017. “Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease”. NATURE COMMUNICATIONS 8 (1): 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., 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(1): 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 8.1 (2017): 678.
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PMID: 25700176
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.
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PMID: 25803835
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PMID: 25803835
Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.
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PMID: 27103069
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PMID: 27103069
B6D2F1 - An improved mouse hybrid strain for the production of ES cell germ line chimeras
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Disruption of the CNTF gene results in motor neuron degeneration.
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Presynaptic localization of Smn and hnRNP R in axon terminals of embryonic and postnatal mouse motoneurons.
Dombert B, Sivadasan R, Simon CM, Jablonka S, Sendtner M., PLoS ONE 9(10), 2014
PMID: 25338097
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PMID: 25338097
An improved perfusion fixation method for the testis.
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PMID: 332010
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Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos.
Wiese S, Herrmann T, Drepper C, Jablonka S, Funk N, Klausmeyer A, Rogers ML, Rush R, Sendtner M., Nat Protoc 5(1), 2009
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PMID: 20057379
Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3.
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PMID: 17534139
Kimura S, Noda T, Yoshimori T., Autophagy 3(5), 2007
PMID: 17534139
PI(5)P regulates autophagosome biogenesis.
Vicinanza M, Korolchuk VI, Ashkenazi A, Puri C, Menzies FM, Clarke JH, Rubinsztein DC., Mol. Cell 57(2), 2015
PMID: 25578879
Vicinanza M, Korolchuk VI, Ashkenazi A, Puri C, Menzies FM, Clarke JH, Rubinsztein DC., Mol. Cell 57(2), 2015
PMID: 25578879
AUTHOR UNKNOWN, 0
Quantitative assessment of tactile allodynia in the rat paw.
Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL., J. Neurosci. Methods 53(1), 1994
PMID: 7990513
Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL., J. Neurosci. Methods 53(1), 1994
PMID: 7990513
AUTHOR UNKNOWN, 0
Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis.
Damme M, Morelle W, Schmidt B, Andersson C, Fogh J, Michalski JC, Lubke T., Mol. Cell. Biol. 30(1), 2010
PMID: 19884343
Damme M, Morelle W, Schmidt B, Andersson C, Fogh J, Michalski JC, Lubke T., Mol. Cell. Biol. 30(1), 2010
PMID: 19884343
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