TY  - JOUR
A1  - Deng, Chunchu
A1  - Reinhard, Sebastian
A1  - Hennlein, Luisa
A1  - Eilts, Janna
A1  - Sachs, Stefan
A1  - Doose, Sören
A1  - Jablonka, Sibylle
A1  - Sauer, Markus
A1  - Moradi, Mehri
A1  - Sendtner, Michael
T1  - Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus-response in spinal muscular atrophy
JF  - Translational Neurodegeneration
N2  - 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 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.
KW  - spinal muscular atrophy
KW  - BDNF stimulation
KW  - dynamics of ribosomal assembly
KW  - presynaptic ER dynamics
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300649
SN  - 2047-9158
VL  - 11
IS  - 1
ER  -