Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons

Keiji Ibata, Maya Kono, Sakae Narumi, Junko Motohashi, Wataru Kakegawa, Kazuhisa Kohda, Michisuke Yuzaki

Research output: Contribution to journalArticle

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 Ca2+-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. Ibata et al. find that Cbln1 is released from lysosomes by neuronal activity and accumulated at axonal boutons of cerebellar granule cells. Co-release of Cbln1 and lysosomal enzymes may serve as a new mechanism of activity-dependent coordinated synapse modification.

Original languageEnglish
Pages (from-to)1184-1198.e10
JournalNeuron
Volume102
Issue number6
DOIs
Publication statusPublished - 2019 Jun 19

Fingerprint

Lysosomes
Cathepsin B
Axons
Synapses
Exocytosis
Presynaptic Receptors
Glutamate Receptors
Neuraminidase
Dendrites
Enzymes

Keywords

  • axon
  • cerebellum
  • granule cell
  • lysosome
  • neurexin
  • Purkinje cell
  • SNARE complex
  • synapse formation
  • tetanus toxin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons. / Ibata, Keiji; Kono, Maya; Narumi, Sakae; Motohashi, Junko; Kakegawa, Wataru; Kohda, Kazuhisa; Yuzaki, Michisuke.

In: Neuron, Vol. 102, No. 6, 19.06.2019, p. 1184-1198.e10.

Research output: Contribution to journalArticle

Ibata, Keiji ; Kono, Maya ; Narumi, Sakae ; Motohashi, Junko ; Kakegawa, Wataru ; Kohda, Kazuhisa ; Yuzaki, Michisuke. / Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons. In: Neuron. 2019 ; Vol. 102, No. 6. pp. 1184-1198.e10.
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