TY  - JOUR
A1  - Franco-Espin, Julio
A1  - Gatius, Alaó
A1  - Armengol, José Ángel
A1  - Arumugam, Saravanan
A1  - Moradi, Mehri
A1  - Sendtner, Michael
A1  - Calderó, Jordi
A1  - Tabares, Lucia
T1  - SMN is physiologically downregulated at wild-type motor nerve terminals but aggregates together with neurofilaments in SMA mouse models
JF  - Biomolecules
N2  - Survival motor neuron (SMN) is an essential and ubiquitously expressed protein that participates in several aspects of RNA metabolism. SMN deficiency causes a devastating motor neuron disease called spinal muscular atrophy (SMA). SMN forms the core of a protein complex localized at the cytoplasm and nuclear gems and that catalyzes spliceosomal snRNP particle synthesis. In cultured motor neurons, SMN is also present in dendrites and axons, and forms part of the ribonucleoprotein transport granules implicated in mRNA trafficking and local translation. Nevertheless, the distribution, regulation, and role of SMN at the axons and presynaptic motor terminals in vivo are still unclear. By using conventional confocal microscopy and STED super-resolution nanoscopy, we found that SMN appears in the form of granules distributed along motor axons at nerve terminals. Our fluorescence in situ hybridization and electron microscopy studies also confirmed the presence of β-actin mRNA, ribosomes, and polysomes in the presynaptic motor terminal, key elements of the protein synthesis machinery involved in local translation in this compartment. SMN granules co-localize with the microtubule-associated protein 1B (MAP1B) and neurofilaments, suggesting that the cytoskeleton participates in transporting and positioning the granules. We also found that, while SMN granules are physiologically downregulated at the presynaptic element during the period of postnatal maturation in wild-type (non-transgenic) mice, they accumulate in areas of neurofilament aggregation in SMA mice, suggesting that the high expression of SMN at the NMJ, together with the cytoskeletal defects, contribute to impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.
KW  - spinal muscular atrophy
KW  - motor neuron degeneration
KW  - SMN granules
KW  - neuromuscular junction
KW  - β-actin mRNA
KW  - MAP1B
KW  - neurofilaments
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290263
SN  - 2218-273X
VL  - 12
IS  - 10
ER  - 
TY  - JOUR
A1  - Tejero, Rocio
A1  - Alsakkal, Mohammad
A1  - Hennlein, Luisa
A1  - Lopez-Cabello, Ana M.
A1  - Jablonka, Sibylle
A1  - Tabares, Lucia
T1  - Nifedipine ameliorates cellular differentiation defects of Smn-deficient motor neurons and enhances neuromuscular transmission in SMA mice
JF  - International Journal of Molecular Sciences
N2  - In spinal muscular atrophy (SMA), mutations in or loss of the Survival Motor Neuron 1 (SMN1) gene reduce full-length SMN protein levels, which leads to the degeneration of a percentage of motor neurons. In mouse models of SMA, the development and maintenance of spinal motor neurons and the neuromuscular junction (NMJ) function are altered. Since nifedipine is known to be neuroprotective and increases neurotransmission in nerve terminals, we investigated its effects on cultured spinal cord motor neurons and motor nerve terminals of control and SMA mice. We found that application of nifedipine increased the frequency of spontaneous Ca\(^{2+}\) transients, growth cone size, cluster-like formations of Cav2.2 channels, and it normalized axon extension in SMA neurons in culture. At the NMJ, nifedipine significantly increased evoked and spontaneous release at low-frequency stimulation in both genotypes. High-strength stimulation revealed that nifedipine increased the size of the readily releasable pool (RRP) of vesicles in control but not SMA mice. These findings provide experimental evidence about the ability of nifedipine to prevent the appearance of developmental defects in SMA embryonic motor neurons in culture and reveal to which extent nifedipine could still increase neurotransmission at the NMJ in SMA mice under different functional demands.
KW  - spinal muscular atrophy
KW  - motor neurons
KW  - synaptic transmission
KW  - neuromuscular junction
KW  - calcium channels
KW  - nifedipine
KW  - growth cone
KW  - axons
KW  - synaptic vesicles
KW  - postsynaptic potentials
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313636
SN  - 1422-0067
VL  - 24
IS  - 8
ER  -