The endoplasmic reticulum promotes microtubule organization and region-specific disassembly to execute Compartmentalized Cell Elimination

Abstract

Specialized cells, such as neurons, die during development and disease. How subcellular organization and interactions across diverse compartments direct death is not well-understood. We examine this by studying the Compartmentalized Cell Elimination (CCE) developmental death program of the C. elegans tail-scaffolding cell (TSC). We find endoplasmic reticulum (ER) shape genes and the microtubule (MT) severase SPAS-1/Spastin, all linked to neurodegeneration, cooperate to promote CCE. Super-resolution imaging reveals profound spatiotemporal dynamics of MTs and the ER across CCE, including enrichment in a stereotyped degenerative node. We observe an ER-dependent non-centrosomal microtubule organizing center (ncMTOC) in the degenerative node, where the ER locally promotes both MT organization and SPAS-1/Spastin-mediated MT severing. The ER is spatially confined, such that SPAS-1/Spastin also has an ER-independent role. Our study expands our understanding of the cell biology of specialized cell death during development and presents molecular links to pathological neurodegeneration, paving the way to neurodegenerative therapies.