Activity-dependent exocytosis of lysosomes regulates structural plasticity of dendritic spines
| Autor: | Padamsey, Z, McGuinness, L, Bardo, S, Reinhart, M, Tong, R, Hedegaard, A, Hart, M, Emptage, N |
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| Rok vydání: | 2016 |
| Zdroj: | Neuron. 93(1) |
| ISSN: | 1097-4199 0896-6273 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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