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A disease causing ATLASTIN 3 mutation affects multiple endoplasmic reticulum-related pathways

Atlastins (ATLs) are membrane-bound GTPases involved in shaping of the endoplasmic reticulum (ER). Mutations in ATL1 and ATL3 cause spastic paraplegia and hereditary sensory neuropathy. We here show that the sensory neuropathy causing ATL3 Y192C mutation reduces the complexity of the tubular ER-netw...

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Detalles Bibliográficos
Autores principales: Behrendt, Laura, Kurth, Ingo, Kaether, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420906/
https://www.ncbi.nlm.nih.gov/pubmed/30666337
http://dx.doi.org/10.1007/s00018-019-03010-x
Descripción
Sumario:Atlastins (ATLs) are membrane-bound GTPases involved in shaping of the endoplasmic reticulum (ER). Mutations in ATL1 and ATL3 cause spastic paraplegia and hereditary sensory neuropathy. We here show that the sensory neuropathy causing ATL3 Y192C mutation reduces the complexity of the tubular ER-network. ATL3 Y192C delays ER-export by reducing the number of ER exit sites, reduces autophagy, fragments the Golgi and causes malformation of the nucleus. In cultured primary neurons, ATL3 Y192C does not localize to the growing axon, resulting in axon growth deficits. Patient-derived fibroblasts possess a tubular ER with reduced complexity and have a reduced number of autophagosomes. The data suggest that the disease-causing ATL3 Y192C mutation affects multiple ER-related pathways, possibly as a consequence of the distorted ER morphology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00018-019-03010-x) contains supplementary material, which is available to authorized users.