TY - JOUR T1 - The structure and global distribution of the endoplasmic reticulum network is actively regulated by lysosomes JF - bioRxiv DO - 10.1101/2020.01.15.907444 SP - 2020.01.15.907444 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 Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/01/16/2020.01.15.907444.abstract N2 - 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. ER -