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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.

Original publication

DOI

10.1016/j.neuron.2016.11.013

Type

Journal article

Journal

Neuron

Publication Date

04/01/2017

Volume

93

Pages

132 - 146

Keywords

MMP-9, TIMP-1, back-propagating action potentials, calcium, dendritic spines, hippocampus, long-term potentiation, lysosome, structural plasticity, synaptic plasticity