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

Nazmiye Özkan, Max Koppers, Inge Soest, Alexandra Harten, Daphne Jurriens, Nalan Liv, Judith Klumperman, Lukas C. Kapitein, Casper C. Hoogenraad and Ginny G. Farías ()
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Nazmiye Özkan: Utrecht University
Max Koppers: Utrecht University
Inge Soest: Utrecht University
Alexandra Harten: Utrecht University
Daphne Jurriens: Utrecht University
Nalan Liv: Utrecht University
Judith Klumperman: Utrecht University
Lukas C. Kapitein: Utrecht University
Casper C. Hoogenraad: Utrecht University
Ginny G. Farías: Utrecht University

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (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.

Date: 2021
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DOI: 10.1038/s41467-021-24713-5

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