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ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability

Nazmiye Özkan, Max Koppers, Inge van Soest, Alexandra van Harten, Nalan Liv, Judith Klumperman, Casper C. Hoogenraad, Ginny G. Farías
doi: https://doi.org/10.1101/2020.06.16.153734
Nazmiye Özkan
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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Max Koppers
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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Inge van Soest
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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Alexandra van Harten
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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Nalan Liv
2Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Judith Klumperman
2Section Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Casper C. Hoogenraad
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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Ginny G. Farías
1Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, The Netherlands
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  • For correspondence: g.c.fariasgaldames@uu.nl
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ABSTRACT

Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the ER and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Lead contact: g.c.fariasgaldames{at}uu.nl

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 16, 2020.
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ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability
Nazmiye Özkan, Max Koppers, Inge van Soest, Alexandra van Harten, Nalan Liv, Judith Klumperman, Casper C. Hoogenraad, Ginny G. Farías
bioRxiv 2020.06.16.153734; doi: https://doi.org/10.1101/2020.06.16.153734
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ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability
Nazmiye Özkan, Max Koppers, Inge van Soest, Alexandra van Harten, Nalan Liv, Judith Klumperman, Casper C. Hoogenraad, Ginny G. Farías
bioRxiv 2020.06.16.153734; doi: https://doi.org/10.1101/2020.06.16.153734

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