Disease-causing mutated ATLASTIN 3 is excluded from distal axons and reduces axonal autophagy

Behrendt, Laura; Hoischen, Christian; Kaether, Christoph

doi:10.1016/j.nbd.2021.105400

Cited by 6 publications

(3 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells were treated with 10 µM of FLI-06 or DMSO (mock treatment, 1:1000) for 24 h before performing immunofluorescence staining for the Golgi protein GolginB1. Microscopic images were acquired with an epifluorescence microscope (Carl Zeiss Microscopy, Axio Imager Z2) and analyzed using Fiji with in-house macros (Behrendt et al, 2021). The number of nuclei (Hoechst-33342) and Golgi fragments per image were quantified and used to calculate the number of Golgi fragments per cell.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A YIPF5-GOT1A/B complex directs a transcription-independent function of ATF6 in ER export

Cramer,

Yonemura,

Behrendt

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Exit from the endoplasmic reticulum is mediated by the Sar1/COPII machinery and a number of accessory factors. How the initial steps of cargo recruitment upstream of Sar1/COPII are mediated remains unclear, but the dihydropyridine FLI-06 inhibits cargo recruitment into ER exit sites. Here, we used chemical genetics screening approaches in conjunction with FLI-06 treatment and identified the ER membrane proteins YIPF5 and GOT1A/B as putative components of early export processes. Surprisingly, the two homologous proteins GOT1A and GOT1B, coded byGOLT1AandGOLT1B, respectively, exhibited opposite functions after treatment with FLI-06: increasing the expression of GOT1A or reducing the expression of GOT1B or YIPF5 prevented inhibition of ER-export by FLI-06. Inhibiting ER export with FLI-06 elicited a specific ER stress-related gene expression signature distinct from the ER-stress signature induced by Thapsigargin. The interactomes of GOT1A and GOT1B suggested a connection to ER-stress mediators. Moreover, RNA-Seq data showed that FLI-06-induced genes are strongly enriched for ATF6 target genes which are suppressed by GOLT1A overexpression or GOLT1B knock-down. This suggests that ATF6 signaling is involved in FLI-06-mediated toxicity, and we could demonstrate that siRNA-mediated knock-down or specific inhibitor of ATF6 rescued cells from FLI-06-mediated cell death. Knock-down or inhibition of ATF6 is sufficient to resume transport from the ER under FLI-06-treatment, suggesting that ATF6 is directly involved in the FLI-06-mediated ER-export block. Surprisingly, our data show that this ATF6 function is independent ofde novotranscription, implying a novel, transcription-independent function of ATF6.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Microscopic images were acquired with an epifluorescence microscope (Carl Zeiss Microscopy, Axio Imager Z2) and analyzed using Fiji with in-house macros (Behrendt et al, 2021). The number of nuclei (Hoechst-33342) and Golgi fragments per image were quantified and used to calculate the number of Golgi fragments per cell.…”

Section: Golgi Fragment Quantificationmentioning

confidence: 99%

A YIPF5-GOT1A/B complex directs a transcription-independent function of ATF6 in ER export

Cramer,

Yonemura,

Behrendt

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…This HSAN subtype can present with lower limb sensory neuropathy and eventual osteomyelitis, and unlike FAM134B‐related HSANII, seldom includes the upper extremities (Hübner & Dikic, 2019; Kornak et al, 2014). ATL3 Y192C induces ER network deformation and reduces the number of axonal autophagosomes and lysosomes (Behrendt et al, 2021; Kornak et al, 2014). Both ATL3 mutations result in impaired ability of ATL3 to adopt a stable dimer confirmation, thereby reducing efficiency of ER membrane fusion and resulting in partial collapse of the ER (Krols et al, 2018).…”

Section: Cytoplasmic Receptorsmentioning

confidence: 99%

ER‐phagy in neurodegeneration

Hill

Sykes

Mellick

2023

J of Neuroscience Research

View full text Add to dashboard Cite

There are many cellular mechanisms implicated in the initiation and progression of neurodegenerative disorders. However, age and the accumulation of unwanted cellular products are a common theme underlying many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Niemann–Pick type C. Autophagy has been studied extensively in these diseases and various genetic risk factors have implicated disruption in autophagy homoeostasis as a major pathogenic mechanism. Autophagy is essential in the maintenance of neuronal homeostasis, as their postmitotic nature makes them particularly susceptible to the damage caused by accumulation of defective or misfolded proteins, disease‐prone aggregates, and damaged organelles. Recently, autophagy of the endoplasmic reticulum (ER‐phagy) has been identified as a novel cellular mechanism for regulating ER morphology and response to cellular stress. As neurodegenerative diseases are generally precipitated by cellular stressors such as protein accumulation and environmental toxin exposure the role of ER‐phagy has begun to be investigated. In this review we discuss the current research in ER‐phagy and its involvement in neurodegenerative diseases.

show abstract

Neuronal endoplasmic reticulum architecture and roles in axonal physiology

Yperman

Kuijpers

2023

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Disease-causing mutated ATLASTIN 3 is excluded from distal axons and reduces axonal autophagy

Cited by 6 publications

References 63 publications

A YIPF5-GOT1A/B complex directs a transcription-independent function of ATF6 in ER export

A YIPF5-GOT1A/B complex directs a transcription-independent function of ATF6 in ER export

ER‐phagy in neurodegeneration

Neuronal endoplasmic reticulum architecture and roles in axonal physiology

Contact Info

Product

Resources

About