Neurons alter endoplasmic reticulum exit sites to accommodate dendritic arbor size

Abstract

Nervous systems exhibit dramatic diversity in cell morphology and size. How neurons regulate their biosynthetic and secretory machinery to support different cell sizes is not well understood. Endoplasmic reticulum exit sites (ERESs) are essential for maintaining secretory flux, and are required for normal dendrite development.1However, it is unknown how neurons of different size regulate the number of secretory structures to accommodate morphogenesis. InC. elegans, we find that 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 in its soma. PVD establishes its high ERES number rapidly after birth, actively maintains ERES number as PVD grows and matures. The initial high number of ERES in PVD is driven by asymmetric cell division producing a large cell size at birth. Subsequent maintenance of ERES number requires the cell fate transcription factor MEC-3 andC. elegansTOR (ceTOR/let-363). ThisceTOR/let-363pathway integrates nutrient availability to coordinate ERES number with soma size and dendritic expansion. Our results are consistent with a model in which transcription factors, master metabolic regulators and nutrient availability coordinate to specify developmental parameters including soma size, ERES number and dendrite size, which together determine neuronal cell fate.