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

作者：Padamsey Zahid; McGuinness Lindsay; Bardo Scott J; Reinhart Marcia; Tong Rudi; Hedegaard Anne; Hart Michael L; Emptage Nigel J^*

来源：Neuron, 2017, 93(1): 132-146.

DOI：10.1016/j.neuron.2016.11.013

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 backpropagating 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.

• 出版日期2017-1-4