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Neuron. 2018 Sep 19;99(6):1216-1232.e7. doi: 10.1016/j.neuron.2018.08.004. Epub 2018 Aug 30.

Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles.

Author information

1
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany.
2
Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany; Max-Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
3
Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany.
4
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany.
5
Max-Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
6
Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany. Electronic address: stephan.sigrist@fu-berlin.de.
7
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany. Electronic address: haucke@fmp-berlin.de.

Abstract

Nervous system function relies on the polarized architecture of neurons, established by directional transport of pre- and postsynaptic cargoes. While delivery of postsynaptic components depends on the secretory pathway, the identity of the membrane compartment(s) supplying presynaptic active zone (AZ) and synaptic vesicle (SV) proteins is unclear. Live imaging in Drosophila larvae and mouse hippocampal neurons provides evidence that presynaptic biogenesis depends on axonal co-transport of SV and AZ proteins in presynaptic lysosome-related vesicles (PLVs). Loss of the lysosomal kinesin adaptor Arl8 results in the accumulation of SV- and AZ-protein-containing vesicles in neuronal cell bodies and a corresponding depletion of SV and AZ components from presynaptic sites, leading to impaired neurotransmission. Conversely, presynaptic function is facilitated upon overexpression of Arl8. Our data reveal an unexpected function for a lysosome-related organelle as an important building block for presynaptic biogenesis.

KEYWORDS:

Drosophila; active zone; axonal transport; hippocampal neurons; lysosomes; neuromuscular junction; neurotransmission; synapse; synaptic vesicle; transport vesicle

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