Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus-response in spinal muscular atrophy
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-300649
- Background: Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential forBackground: Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn (survival of motor neuron) deficiency that could contribute to axonopathy and presynaptic dysfunction in SMA. Methods: Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation. Results: We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In addition, in axon terminals of Smn-deficient motoneurons, ribosomes failed to respond to the brain-derived neurotrophic factor stimulation, and did not undergo rapid association with the axonal ER in response to extracellular stimuli. Conclusions: These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.…
Autor(en): | Chunchu Deng, Sebastian Reinhard, Luisa Hennlein, Janna Eilts, Stefan Sachs, Sören Doose, Sibylle Jablonka, Markus Sauer, Mehri Moradi, Michael Sendtner |
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URN: | urn:nbn:de:bvb:20-opus-300649 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Klinische Neurobiologie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Translational Neurodegeneration |
ISSN: | 2047-9158 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 1 |
Aufsatznummer: | 31 |
Originalveröffentlichung / Quelle: | Translational Neurodegeneration 2022, 11(1):31. DOI: 10.1186/s40035-022-00304-2 |
DOI: | https://doi.org/10.1186/s40035-022-00304-2 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | BDNF stimulation; dynamics of ribosomal assembly; presynaptic ER dynamics; spinal muscular atrophy |
Datum der Freischaltung: | 27.02.2023 |
Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |