PT  - JOURNAL ARTICLE
AU  - Meng Lu
AU  - Francesca W. van Tartwijk
AU  - Julie Qiaojin Lin
AU  - Wilco Nijenhuis
AU  - Pierre Parutto
AU  - Marcus Fantham
AU  - Charles N. Christensen
AU  - Edward Avezov
AU  - Christine E. Holt
AU  - Alan Tunnacliffe
AU  - David Holcman
AU  - Lukas C. Kapitein
AU  - Gabriele Kaminski Schierle
AU  - Clemens F. Kaminski
TI  - The structure and global distribution of the endoplasmic reticulum network is actively regulated by lysosomes
AID  - 10.1101/2020.01.15.907444
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.15.907444
4099  - http://biorxiv.org/content/early/2020/01/16/2020.01.15.907444.short
4100  - http://biorxiv.org/content/early/2020/01/16/2020.01.15.907444.full
AB  - The endoplasmic reticulum (ER) comprises morphologically and functionally distinct domains, sheets and interconnected tubules. These domains undergo dynamic reshaping, in response to changes in the cellular environment. However, the mechanisms behind this rapid remodeling within minutes are largely unknown. Here, we report that ER remodeling is actively driven by lysosomes, following lysosome repositioning in response to changes in nutritional status. The anchorage of lysosomes to ER growth tips is critical for ER tubule elongation and connection. We validate this causal link via the chemo- and optogenetically driven re-positioning of lysosomes, which leads to both a redistribution of the ER tubules and its global morphology. Lysosomes sense metabolic change in the cell and regulate ER tubule distribution accordingly. Dysfunction in this mechanism during axonal extension may lead to axonal growth defects. Our results demonstrate a critical role of lysosome-regulated ER dynamics and reshaping in nutrient responses and neuronal development.