Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.
Padamsey Z., McGuinness L., Bardo SJ., Reinhart M., Tong R., Hedegaard A., Hart ML., Emptage NJ.
Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca(2+) stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca(2+) release from lysosomes in the dendrites. This Ca(2+) release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca(2+) signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling.