Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites

Xianzhuang Liu,Fei Sun,Kang Shen,Liling Niu,Junjie Hu,Xiangming Wang,Xixia Li,Xiangyang Guo

doi:10.1038/s41467-019-08478-6

Abstract

Endoplasmic reticulum (ER) is characterized by interconnected tubules and sheets. Neuronal ER adopts specific morphology in axons, dendrites and soma. Here we study mechanisms underlying ER morphogenesis in a C. elegans sensory neuron PVD. In PVD soma and dendrite branch points, ER tubules connect to form networks. ER tubules fill primary dendrites but only extend to some but not all dendritic branches. We find that the Atlastin-1 ortholog, atln-1 is required for neuronal ER morphology. In atln-1 mutants with impaired GTPase activity, ER networks in soma and dendrite branch points are reduced and replaced by tubules, and ER tubules retracted from high-order dendritic branches, causing destabilized microtubule in these branches. The abnormal ER morphology likely causes defects in mitochondria fission at dendritic branch points. Mutant alleles of Atlastin-1 found in Hereditary Spastic Paraplegia (HSP) patients show similar ER phenotypes, suggesting that neuronal ER impairment contributes to HSP disease pathogenesis.

Highlights

Endoplasmic reticulum (ER) is characterized by interconnected tubules and sheets
In this study, we use the C. elegans sensory neuron PVD to understand how cell type specific ER morphology is established in dendrites and whether the specific morphology is related to its function in neurons
First; we systemically examine the ER morphology and dynamics in dendrites in vivo

Summary

Introduction

Neuronal ER adopts specific morphology in axons, dendrites and soma. In PVD soma and dendrite branch points, ER tubules connect to form networks. We find that the Atlastin-1 ortholog, atln-1 is required for neuronal ER morphology. In atln-1 mutants with impaired GTPase activity, ER networks in soma and dendrite branch points are reduced and replaced by tubules, and ER tubules retracted from high-order dendritic branches, causing destabilized microtubule in these branches. The abnormal ER morphology likely causes defects in mitochondria fission at dendritic branch points. 1234567890():,; The endoplasmic reticulum (ER) forms a continuous intracellular membrane system, consisting of the nuclear envelope, flat sheets, and elaborate network of tubules throughout cytoplasm[1,2]. The ER localized dynamin-like GTPase Atlastin-1 (ATL) promotes the fusion between tubules to form ER networks[7,8]. 63, Kinectin, p180, Lunapark, and Protrudin have been implicated in establishment and maintenance of ER morphology[10,11,12]

Methods

Results

Conclusion