Ftd/Als Type 7–Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator, in N1E-115 Cells

Published: June 19, 2023

Frontotemporal dementia and/or amyotrophic lateral sclerosis type 7 (FTD/ALS7) is an autosomal dominant neurodegenerative disorder characterized by the onset of ALS FTD mainly in adulthood. Patients with some types mutations, including Thr104Asn (T104N) mutation charged multivesicular body protein 2B (CHMP2B), have predominantly phenotypes, whereas patients other mutations phenotypes. A few further both phenotypes approximately equally; however, reason why differ depending on position unknown. CHMP2B composes one part endosomal sorting complexes required for transport (ESCRT), specifically ESCRT-III, cytoplasm. We describe here, first time, that T104N inhibits neuronal process elongation N1E-115 cell line, a model differentiation. The inhibitory phenotype was accompanied changes marker expression. It noteworthy but not its wild-type preferentially accumulated Golgi body. Of four major stress signaling pathways currently known, pathway through Arf4, as small GTPase, upregulated cells expressing mutation. Conversely, knockdown Arf4 cognate interfering (si)RNA recovered inhibited These results suggest morphological differentiation triggering signaling, revealing possible therapeutic molecular target recovering potential and cellular underlying FTD/ALS7.

Language: Английский

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Non-autophagic Golgi-LC3 lipidation facilitates TFE3 stress response against Golgi dysfunction

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(21), P. 5085 - 5113

Published: Sept. 16, 2024

Abstract Lipidated ATG8/LC3 proteins are recruited to single membrane compartments as well autophagosomes, supporting their functions. Although recent studies have shown that Golgi-LC3 lipidation follows Golgi damage, its molecular mechanism and function under stress remain unknown. Here, by combining DLK1 overexpression a new strategy for induction of Golgi-specific LC3 lipidation, the application Golgi-damaging reagents, we unravel role lipidation. Upon overexpression, is lipidated on apparatus in an ATG12-ATG5-ATG16L1 complex-dependent manner; post-Golgi trafficking blockade primary cause this During stress, ATG16L1 through interaction with V-ATPase After inhibition, TFE3, key regulator response, translocated nucleus. Defects disrupt translocation, leading attenuation response. Together, our results reveal unexplored

Language: Английский

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A NEAT Discovery Hints at Altered Golgi Signaling in Lung Fibrosis

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2023, Volume and Issue: 70(3), P. 155 - 156

Published: Dec. 7, 2023

"A NEAT Discovery Hints at Altered Golgi Signaling in Lung Fibrosis." American Journal of Respiratory Cell and Molecular Biology, 0(ja), pp.

Language: Английский

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