Learn More
Exocytosis, the fusion of secretory vesicles with the plasma membrane to allow release of the contents of the vesicles into the extracellular environment, and endocytosis, the internalization of these vesicles to allow another round of secretion, are coupled. It is, however, uncertain whether exocytosis and endocytosis are tightly coupled, such that(More)
Cysteine string protein alpha (CSPalpha)--an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones--is thought to regulate Ca2+ channels and/or synaptic vesicle exocytosis. We now show that, in young mice, deletion of CSPalpha does not impair survival and causes no significant changes in presynaptic Ca2+ currents(More)
Low levels of survival motor neuron (SMN) protein result in spinal muscular atrophy (SMA), a severe genetic disease characterized by motor impairment and premature lethality. Although SMN is a ubiquitous protein, motor neurons are much more vulnerable to low levels of SMN than other cells. To gain insight into the pathogenesis of SMA, we have compared(More)
Cysteine string protein (CSP) alpha is an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40-type cochaperones. Previous studies showed that deletion of CSPalpha in mice leads to massive lethal neurodegeneration but did not clarify how the neurodegeneration affects specific subpopulations of neurons. Here, we analyzed the(More)
F-actin bundling plastin 3 (PLS3) is a fully protective modifier of the neuromuscular disease spinal muscular atrophy (SMA), the most common genetic cause of infant death. The generation of a conditional PLS3-over-expressing mouse and its breeding into an SMA background allowed us to decipher the exact biological mechanism underlying PLS3-mediated SMA(More)
Synchronous neurotransmitter release is a highly regulated process that takes place at specializations at the presynaptic membrane called active zones (AZs). The relationships between AZs, quantal release, and vesicle replenishment are not well understood in a mature synapse. We have measured the number, distribution, and other properties of AZs in mouse(More)
We monitored presynaptic exocytosis and vesicle recycling at neuromuscular junctions of transgenic mice expressing synaptopHluorin (spH), using simultaneous optical and electrophysiological recordings. Synaptic transmission was indistinguishable from that in wild-type controls. Fluorescence rose during and decayed monotonically after stimulus trains to the(More)
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(More)