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Cited by 186Neuroscience and Neuropharmacology ResearchCellular transport and secretionCalcium signaling and nucleotide metabolism

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

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Padamsey, Zahid, McGuinness, Lindsay, Bardo, Scott J., Reinhart, Marcia, Tong, Rudi, Hedegaard, Anne, Hart, Michael L., Emptage, Nigel J.·2017·Neuron
DOI 10.1016/j.neuron.2016.11.013PMC PMC5222721
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Abstract

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ 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 Ca 2+ 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.

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  • Cathepsins have preferred cleavage sites and differentially cleave neurodegenerative disease proteins such as tau, TDP-43, and alpha-synuclein.

    “Even within the three cathepsin families, cathepsins each have preferred cleavage sites which are apparent in how they differentially cleave neurodegenerative disease proteins such as tau, TDP-43, and alpha-synuclein.124”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [124]

    The Results section, “Lysosomal Fusion Results in the Release of Cathepsin B” (page unavailable), identifies cathepsins as proteases, and “Cathepsin B Release Activates MMP-9” describes Cathepsin B cleaving TIMP-1. Our copy does not address preferred cleavage sites or differential cleavage of tau, TDP-43, and alpha-synuclein (searched for those proteins and cleavage specificity). (LLM, conf=0.75)

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Cited by

Sorted by citations

Authors
Padamsey, Z., McGuinness, L., Bardo, S. J., Reinhart, M., Tong, R., Hedegaard, A., Hart, M. L., & Emptage, N. J.
Affiliations
University of Oxford (GB)
Corresponding author
Emptage, Nigel J.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2017-01
Volume
93
Issue
1
Pages
132-146
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2016.11.013
PMC
PMC5222721
OpenAlex
W2561801775
Cited by
186
References
3
Citations by year
2026: 9 · 2025: 21 · 2024: 20 · 2023: 15 · 2022: 25 · 2021: 26 · 2020: 17 · 2019: 13 · 2018: 26 · 2017: 14
FWCI
9.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
Funders
  • MRC (G0501572)
  • BBSRC (BB/5018724/1)
  • Magdalen College, Oxford
  • Rhodes Trust
  • British Pharmacological Society
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
lysosomes, exocytosis, dendritic spines, cathepsin B, MMP-9, extracellular matrix remodeling, backpropagating action potentials, hippocampal pyramidal neurons, synaptic plasticity
MeSH terms
Animals, Calcium, Cathepsin B, Dendrites, Exocytosis, Hippocampus, Lysosomes, Male, Neuronal Plasticity, Signal Transduction, Rats, Wistar, Pyramidal Cells, Patch-Clamp Techniques, Matrix Metalloproteinase 9, Dendritic Spines, Rats

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