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Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons.
- Source :
-
Neuron [Neuron] 2019 Jun 19; Vol. 102 (6), pp. 1184-1198.e10. Date of Electronic Publication: 2019 May 06. - Publication Year :
- 2019
-
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 <superscript>2+</superscript> -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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Axons drug effects
Cathepsin B metabolism
Cerebellum cytology
Dendrites metabolism
Exocytosis drug effects
In Vitro Techniques
Metalloendopeptidases pharmacology
Mice
Neuraminidase genetics
Neuraminidase metabolism
Neuronal Plasticity
Presynaptic Terminals metabolism
Purkinje Cells metabolism
Receptors, Glutamate metabolism
Tetanus Toxin pharmacology
Axons metabolism
Cell Adhesion Molecules, Neuronal metabolism
Exocytosis physiology
Lysosomes metabolism
Nerve Tissue Proteins metabolism
Neurons metabolism
Protein Precursors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 102
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 31072786
- Full Text :
- https://doi.org/10.1016/j.neuron.2019.03.044