Neuron
Volume 93, Issue 1, 4 January 2017, Pages 132-146
Journal home page for Neuron

Article
Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines

https://doi.org/10.1016/j.neuron.2016.11.013Get rights and content
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Highlights

  • Back-propagating action potentials induce Ca2+ release from lysosomes in neurons

  • Lysosomal Ca2+ release triggers exocytosis of the lysosomal protease Cathepsin B

  • Cathepsin B maintains activity-dependent dendritic spine growth by activating MMP-9

Summary

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca2+ release from lysosomes in the dendrites. This Ca2+ 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 Ca2+ 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.

Keywords

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

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