The unfolded protein response is required for dendrite morphogenesis.

Xing Wei,Caitlin A Taylor,Jianqi Zhang,Audrey S Howell,Kang Shen,Xintong Dong,Wei Zou,Roshni C Cooper,David R Sherwood

doi:10.7554/elife.06963

Abstract

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors.

Highlights

The organization of dendritic arbors is fundamental to the shape and connectivity of the nervous system (Ramon y Cajal, 1911; Wassle et al, 1981)
We investigated whether the regulated Ire1-dependent decay (RIDD) pathway functions in parallel with XBP-1 to regulate dendrite morphogenesis. mRNA degradation is initiated by internal cleavage mediated by RIDD, and the resulting RNA fragments would be subject to degradation by cytoplasmic 5′-3′ mRNA degradation machinery
The unfolded protein response is an intrinsic requirement for highly branched neurons Conserved in all eukaryotes, the UPR pathway plays significant roles in dealing with cellular stress and balancing homeostasis and apoptosis (Walter and Ron, 2011)

Summary

Introduction

The organization of dendritic arbors is fundamental to the shape and connectivity of the nervous system (Ramon y Cajal, 1911; Wassle et al, 1981). Several diffusive or cell-surface molecules play instructive roles in guiding the growth and patterning of dendritic arbors. One common feature for dendrite development is that the sister branches from the same neuron avoid each other, while coexist with the branches of their neighboring neurons. This self-avoidance phenomenon has been elegantly elucidated by the function of two classes of highly diversified, contact-mediated repulsive molecules: Down syndrome cell adhesion molecules in Drosophila and protocadherins in vertebrates (Schmucker et al, 2000; Wojtowicz et al, 2004; Matthews et al, 2007; Lefebvre et al, 2012)

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