Activity-dependent exocytosis of lysosomes regulates structural plasticity of dendritic spines

Journal article

Lysosomes have traditionally been viewed as degradative organelles, though 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+ signalling 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.

Authors: Padamsey, Z; McGuinness, L; Bardo, S; Reinhart, M; Tong, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Neuron
• Volume: 93
• Issue: 1
• Pages: 132-146
• Publication date: 2016-12-15
• Acceptance date: 2016-10-31
• DOI: 10.1016/j.neuron.2016.11.013
• EISSN: 1097-4199
• ISSN: 0896-6273
• Keywords: Article