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 DOI Open Access

Remina Shirai,

M. Cho,

Mikinori Isogai

et al.

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

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 DOI Open Access

Remina Shirai,

M. Cho,

Mikinori Isogai

et al.

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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