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

Zahid Padamsey, Lindsay McGuinness, Scott J. Bardo, Marcia Reinhart, Rudi Tong, Anne Hedegaard, Michael L. Hart, Nigel J. Emptage

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)132-146
Number of pages15
Issue number1
Early online date15 Dec 2016
Publication statusPublished - 4 Jan 2017


  • Animals
  • Calcium/metabolism
  • Cathepsin B/metabolism
  • Dendrites/metabolism
  • Dendritic Spines/metabolism
  • Exocytosis/physiology
  • Hippocampus/cytology
  • Lysosomes/metabolism
  • Male
  • Matrix Metalloproteinase 9/metabolism
  • Neuronal Plasticity/physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells/cytology
  • Rats
  • Rats, Wistar
  • Signal Transduction


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