Activity-dependent exocytosis of dendritic lysosomes regulates structural plasticity Event
For more information regarding this event, please telephone Kim Lipscombe on 02380597747 or email K.R.Lipscombe@soton.ac.uk .
Event details
This talk is part of the Centre for Biological Sciences Invited Speaker Series. Open to all.
Lysosomes are traditionally viewed as the cell’s dustbin, although recent studies have revealed that they also function as Ca2+ stores. In this presentation I will present data that reveal that action potentials propagating within neuronal dendrites (bpAPs) are able to elicit Ca2+ release from dendritic lysosomes in CA3 and CA1 pyramidal neurons. Using a novel pHlourin, I will show that Ca2+ release triggers fusion of lysosomes with the plasma membrane, liberating lysosomal proteases into the extracelluar space. These proteases increase the activity of extracellular matrix metalloproteinases, (canonically linked to extracellular matrix remodeling) with cathepsin B, in particular, elevating MMP9 activity. Inhibition of either lysosomal fusion or cathepsin B impairs activity-dependent growth of dendritic spines induced by Hebbian pairing of synaptic activity with bpAPs; these impairments can be rescued by exogenous application of either active cathepsin B or MMP9. These findings reveal a surprising but essential role of lysosomes in the activity-dependent regulation of structural plasticity.
Speaker information
Professor Nigel Emtage ,University of Oxford,Lecturer in Synaptic Pharmacology