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The structure and global distribution of the endoplasmic reticulum network are actively regulated by lysosomes

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 are largely unknown. Here, w...

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Detalles Bibliográficos
Autores principales: Lu, Meng, van Tartwijk, Francesca W., Lin, Julie Qiaojin, Nijenhuis, Wilco, Parutto, Pierre, Fantham, Marcus, Christensen, Charles N., Avezov, Edward, Holt, Christine E., Tunnacliffe, Alan, Holcman, David, Kapitein, Lukas, Schierle, Gabriele S. Kaminski, Kaminski, Clemens F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744115/
https://www.ncbi.nlm.nih.gov/pubmed/33328230
http://dx.doi.org/10.1126/sciadv.abc7209
Descripción
Sumario: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 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 repositioning of lysosomes, which leads to both a redistribution of the ER tubules and a change of its global morphology. Therefore, 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.