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

Özkan, Nazmiye, Koppers, Max, van Soest, Inge, van Harten, Alexandra, Jurriens, Daphne, Liv, Nalan, Klumperman, Judith, Kapitein, Lukas C., Hoogenraad, Casper C., Farías, Ginny G.·2021·Nature Communications
DOI 10.1038/s41467-021-24713-5PMC PMC8302662

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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.

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  • The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated.

    “The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated, and the number and composition of lysosomes differ between the proximal axon and the distal axon (Farias et al., 2017b;Ozkan et al., 2021).”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Ozkan et al., 2021

  • The number and composition of lysosomes differ between the proximal axon and the distal axon.

    “The entry of cargo (including lysosomes) into the axon at the proximal axon and the axon initial segment (AIS) is tightly regulated, and the number and composition of lysosomes differ between the proximal axon and the distal axon (Farias et al., 2017b;Ozkan et al., 2021).”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Ozkan et al., 2021

    The Results section, “ER shape regulates lysosome availability in the axon” (page unavailable), counts lysosomes in a proximal-axon segment and describes their distribution along the axon. A search for proximal-versus-distal comparisons found no passage establishing that lysosome number or composition differs between those regions. (LLM, conf=0.72)

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Metadata

Authors
Özkan, N., Koppers, M., van Soest, I., van Harten, A., Jurriens, D., Liv, N., Klumperman, J., Kapitein, L. C., Hoogenraad, C. C., & Farías, G. G.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-07-23
Volume
12
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-021-24713-5
PMC
PMC8302662
Cited by
69
References
1
Language
en
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