RRC ID |
59375
|
著者 |
Liu X, Guo X, Niu L, Li X, Sun F, Hu J, Wang X, Shen K.
|
タイトル |
Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites.
|
ジャーナル |
Nat Commun
|
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.
|
巻・号 |
10(1)
|
ページ |
568
|
公開日 |
2019-2-4
|
DOI |
10.1038/s41467-019-08478-6
|
PII |
10.1038/s41467-019-08478-6
|
PMID |
30718476
|
PMC |
PMC6362286
|
MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Dendrites / genetics
Dendrites / metabolism*
Endoplasmic Reticulum / genetics
Endoplasmic Reticulum / metabolism*
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism
Microtubules / metabolism
Spastic Paraplegia, Hereditary / genetics
Spastic Paraplegia, Hereditary / metabolism
|
IF |
11.878
|
引用数 |
5
|
リソース情報 |
線虫 |
tm3667
tm683
tm390 |