Neurons alter endoplasmic reticulum exit sites to accommodate dendritic arbor size

Abstract

AbstractNervous systems exhibit dramatic diversity in cell morphology and size. How neurons regulate their biosynthetic and secretory machinery to support such diversity is not well understood. Endoplasmic reticulum exit sites (ERESs) are essential for maintaining secretory flux, and are required for normal dendrite development, but how neurons of different size regulate secretory capacity remains unknown. InC. elegans, wefind that the ERES number is strongly correlated with the size of a neuron’s dendritic arbor. The elaborately branched sensory neuron, PVD, has especially high ERES numbers. Asymmetric cell division provides PVD with a large initial cell size critical for rapid establishment of PVD’s high ERES number before neurite outgrowth, and these ERESs are maintained throughout development. Maintenance of ERES number requires the cell fate transcription factor MEC-3,C. elegansTOR (ceTOR/let-363), and nutrient availability, withmec-3andceTOR/let-363mutant PVDs both displaying reductions in ERES number, soma size, and dendrite size. Notably,mec-3mutant animals exhibit reduced expression of aceTOR/let-363reporter in PVD, and starvation reduces ERES number and somato-dendritic size in a manner genetically redundant withceTOR/let-363perturbation. Our data suggest that both asymmetric cell division and nutrient sensing pathways regulate secretory capacities to support elaborate dendritic arbors.