Altered GM1 catabolism affects NMDAR-mediated Ca2+ signaling at ER-PM junctions and increases synaptic spine formation in a GM1-gangliosidosis model
Weesner et al. find that, in GM1-gangliosidosis mice, neuronal accumulation of GM1 at the ER-PM junctions alters NMDAR-mediated Ca2+ signaling and activates the synaptogenesis pathway via ERK signaling. This leads to increased synaptic spine density without an increase in synaptic connectivity, contributing to the neurodegeneration characteristic of the disease.