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Cited by 56Neuroscience and Neuropharmacology ResearchCellular transport and secretionGenetics and Neurodevelopmental Disorders

Activity-dependent secretion of synaptic organizer Cbln1 from lysosomes in granule cell axons

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Ibata, Keiji, Kono, Maya, Narumi, Sakae, Motohashi, Junko, Kakegawa, Wataru, Kohda, Kazuhisa, Yuzaki, Michisuke·2019·Neuron
DOI 10.1016/j.neuron.2019.03.044
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Abstract

Synapse formation is achieved by various synaptic organizers. Although this process is highly regulated by neuronal activity, the underlying molecular mechanisms remain largely unclear. Here we show that Cbln1, a synaptic organizer of the C1q family, is released from lysosomes in axons but not dendrites of cerebellar granule cells in an activity- and Ca 2+-dependent manner. Exocytosed Cbln1 was retained on axonal surfaces by binding to its presynaptic receptor neurexin. Cbln1 further diffused laterally along the axonal surface and accumulated at boutons by binding postsynaptic δ2 glutamate receptors. Cbln1 exocytosis was insensitive to tetanus neurotoxin, accompanied by cathepsin B release, and decreased by disrupting lysosomes. Furthermore, overexpression of lysosomal sialidase Neu1 not only inhibited Cbln1 and cathepsin B exocytosis in vitro but also reduced axonal bouton formation in vivo. Our findings imply that co-release of Cbln1 and cathepsin B from lysosomes serves as a new mechanism of activity-dependent coordinated synapse modification.

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  • This led to the identification of some of the earliest disease-associated genes, including APP, PS1 and PS2 in AD, SNCA and LRRK2 in PD and MAPT and GRN in FTD.

    “This subsequently led to the identification of some of the earliest disease-associated genes, including APP, PS1 and PS2 in AD, SNCA and LRRK2 in PD and MAPT and GRN in FTD.79–87”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [79]

    The supplied passages and searches for APP, PS1, PS2, SNCA, LRRK2, MAPT, GRN, and early disease-gene identification found no passage addressing the claim. The paper instead discusses activity-dependent Cbln1 release from granule cells (Abstract; page unavailable). (LLM, conf=0.78)

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  • Heterozygous progranulin (GRN) mutations are associated with FTD with TDP-43 Type A pathology.

    “Heterozygous progranulin (GRN) mutations are associated with FTD with TDP-43 Type A pathology.79,111”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [79]

    The supplied Results and Discussion passages address Cbln1 secretion and cerebellar synapse formation, not progranulin mutations or FTD pathology. Searches for heterozygous GRN mutations, frontotemporal dementia, and TDP-43 Type A pathology found no passage in our copy addressing the claimed association. (LLM, conf=0.76)

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Cited by

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Authors
Ibata, K., Kono, M., Narumi, S., Motohashi, J., Kakegawa, W., Kohda, K., & Yuzaki, M.
Affiliations
  • St. Marianna University School of Medicine (JP)
  • Keio University (JP)
Corresponding author
Yuzaki, Michisuke
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2019-06
Volume
102
Issue
6
Pages
1184-1198.e10
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2019.03.044
OpenAlex
W2943033141
Cited by
56
References
2
Citations by year
2026: 6 · 2025: 9 · 2024: 2 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 8 · 2019: 2
FWCI
3.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (15H05772, 16H06461, 16K13107)
  • Core Research for Evolutional Science and Technology
  • Japan Science and Technology Agency (JPMJCR1854)
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 › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Cbln1, synaptic organizer, lysosomal exocytosis, cerebellar granule cells, axons, activity-dependent synaptic plasticity, cathepsin B, neurexin, presynaptic receptors, calcium-dependent secretion
MeSH terms
Animals, Axons, Cathepsin B, Cerebellum, Dendrites, Exocytosis, Lysosomes, Metalloendopeptidases, Nerve Tissue Proteins, Neuraminidase, Neuronal Plasticity, Neurons, Protein Precursors, Purkinje Cells, Tetanus Toxin, Cell Adhesion Molecules, Neuronal, Receptors, Glutamate, Presynaptic Terminals, Mice, In Vitro Techniques

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