SMN requirement for synaptic vesicle, active zone and microtubule postnatal organization in motor nerve terminals.
Low levels of the Survival Motor Neuron (SMN) protein produce Spinal Muscular Atrophy (SMA), a severe monogenetic disease in infants characterized by muscle weakness and impaired synaptic transmission. We report here severe structural and functional alterations in the organization of the organelles and the cytoskeleton of motor nerve terminals in a mouse model of SMA. The decrease in SMN levels resulted in the clustering of synaptic vesicles (SVs) and Active Zones (AZs), reduction in the size of the readily releasable pool (RRP), and the recycling pool (RP) of synaptic vesicles, a decrease in active mitochondria and limiting of neurofilament and microtubule maturation. We propose that SMN is essential for the normal postnatal maturation of motor nerve terminals and that SMN deficiency disrupts the presynaptic organization leading to neurodegeneration.
Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville, Spain.
Laura
L
Torres-Benito
Margret Feodora
MF
Neher
Raquel
R
Cano
Rocio
R
Ruiz
Lucia
L
Tabares
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D016000:Cluster Analysis; D051379:Mice; D008870:Microtubules / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism* / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D055533:Survival of Motor Neuron 1 Protein