TFG-related neurologic disorders: New insights into relationships between endoplasmic reticulum and neurodegeneration

Takuya Yagi, Daisuke Ito, Norihiro Suzuki

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The tropomyosin-receptor kinase fused gene (TFG), which is located on chromosome 3q12.2, was originally identified as a fusion partner that results in the formation of oncogenic products associated with multiple cancers. TFG protein interacts directly with Sec16, the scaffolding protein for coat protein II-coated vesicles that regulate endoplasmic reticulum (ER)-to-Golgi transport at ER exit sites. In 2012, a heterozygous mutation of TFG was identified as the causative gene for autosomal-dominant hereditary motor and sensory neuropathy with proximal dominant involvement. In 2013, a homozygous mutation of TFG was reported in a family with early onset spastic paraplegia, optic atrophy, and neuropathy. Another novel mutation in TFG was discovered in 2014 as a cause of dominant axonal Charcot-Marie-Tooth disease type 2. These findings suggest that mutations of TFG cause ER dysfunction and neurodegeneration in this disease spectrum, which is tightly associated with ER function. Here, we review the clinical phenotypes of these diseases and present recent insights that suggest causal roles of ER dysfunction in TFG-related neurologic disorders. Although the precise pathogenetic mechanisms underlying these TFG mutations remain to be elucidated, experimental manipulations suggest that the dysregulations of ER homeostasis that occur due to mutations in TFG lead to neurodegeneration.

Original languageEnglish
Pages (from-to)299-305
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number4
DOIs
Publication statusPublished - 2016

Fingerprint

Nervous System Diseases
Endoplasmic Reticulum
Genes
Mutation
Hereditary Sensory and Motor Neuropathy
Coated Vesicles
Charcot-Marie-Tooth Disease
tropomyosin kinase
Dominant Genes
Capsid Proteins
Proteins
Homeostasis
Chromosomes
Phenotype

Keywords

  • Charcot-Marie-Tooth disease
  • Endoplasmic reticulum
  • Neurodegeneration
  • Spastic paraplegia
  • Tropomyosin-receptor kinase fused gene (TFG)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

TFG-related neurologic disorders : New insights into relationships between endoplasmic reticulum and neurodegeneration. / Yagi, Takuya; Ito, Daisuke; Suzuki, Norihiro.

In: Journal of Neuropathology and Experimental Neurology, Vol. 75, No. 4, 2016, p. 299-305.

Research output: Contribution to journalArticle

@article{acd905d7d028440a9d8258c7d227d767,
title = "TFG-related neurologic disorders: New insights into relationships between endoplasmic reticulum and neurodegeneration",
abstract = "The tropomyosin-receptor kinase fused gene (TFG), which is located on chromosome 3q12.2, was originally identified as a fusion partner that results in the formation of oncogenic products associated with multiple cancers. TFG protein interacts directly with Sec16, the scaffolding protein for coat protein II-coated vesicles that regulate endoplasmic reticulum (ER)-to-Golgi transport at ER exit sites. In 2012, a heterozygous mutation of TFG was identified as the causative gene for autosomal-dominant hereditary motor and sensory neuropathy with proximal dominant involvement. In 2013, a homozygous mutation of TFG was reported in a family with early onset spastic paraplegia, optic atrophy, and neuropathy. Another novel mutation in TFG was discovered in 2014 as a cause of dominant axonal Charcot-Marie-Tooth disease type 2. These findings suggest that mutations of TFG cause ER dysfunction and neurodegeneration in this disease spectrum, which is tightly associated with ER function. Here, we review the clinical phenotypes of these diseases and present recent insights that suggest causal roles of ER dysfunction in TFG-related neurologic disorders. Although the precise pathogenetic mechanisms underlying these TFG mutations remain to be elucidated, experimental manipulations suggest that the dysregulations of ER homeostasis that occur due to mutations in TFG lead to neurodegeneration.",
keywords = "Charcot-Marie-Tooth disease, Endoplasmic reticulum, Neurodegeneration, Spastic paraplegia, Tropomyosin-receptor kinase fused gene (TFG)",
author = "Takuya Yagi and Daisuke Ito and Norihiro Suzuki",
year = "2016",
doi = "10.1093/jnen/nlw009",
language = "English",
volume = "75",
pages = "299--305",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - TFG-related neurologic disorders

T2 - New insights into relationships between endoplasmic reticulum and neurodegeneration

AU - Yagi, Takuya

AU - Ito, Daisuke

AU - Suzuki, Norihiro

PY - 2016

Y1 - 2016

N2 - The tropomyosin-receptor kinase fused gene (TFG), which is located on chromosome 3q12.2, was originally identified as a fusion partner that results in the formation of oncogenic products associated with multiple cancers. TFG protein interacts directly with Sec16, the scaffolding protein for coat protein II-coated vesicles that regulate endoplasmic reticulum (ER)-to-Golgi transport at ER exit sites. In 2012, a heterozygous mutation of TFG was identified as the causative gene for autosomal-dominant hereditary motor and sensory neuropathy with proximal dominant involvement. In 2013, a homozygous mutation of TFG was reported in a family with early onset spastic paraplegia, optic atrophy, and neuropathy. Another novel mutation in TFG was discovered in 2014 as a cause of dominant axonal Charcot-Marie-Tooth disease type 2. These findings suggest that mutations of TFG cause ER dysfunction and neurodegeneration in this disease spectrum, which is tightly associated with ER function. Here, we review the clinical phenotypes of these diseases and present recent insights that suggest causal roles of ER dysfunction in TFG-related neurologic disorders. Although the precise pathogenetic mechanisms underlying these TFG mutations remain to be elucidated, experimental manipulations suggest that the dysregulations of ER homeostasis that occur due to mutations in TFG lead to neurodegeneration.

AB - The tropomyosin-receptor kinase fused gene (TFG), which is located on chromosome 3q12.2, was originally identified as a fusion partner that results in the formation of oncogenic products associated with multiple cancers. TFG protein interacts directly with Sec16, the scaffolding protein for coat protein II-coated vesicles that regulate endoplasmic reticulum (ER)-to-Golgi transport at ER exit sites. In 2012, a heterozygous mutation of TFG was identified as the causative gene for autosomal-dominant hereditary motor and sensory neuropathy with proximal dominant involvement. In 2013, a homozygous mutation of TFG was reported in a family with early onset spastic paraplegia, optic atrophy, and neuropathy. Another novel mutation in TFG was discovered in 2014 as a cause of dominant axonal Charcot-Marie-Tooth disease type 2. These findings suggest that mutations of TFG cause ER dysfunction and neurodegeneration in this disease spectrum, which is tightly associated with ER function. Here, we review the clinical phenotypes of these diseases and present recent insights that suggest causal roles of ER dysfunction in TFG-related neurologic disorders. Although the precise pathogenetic mechanisms underlying these TFG mutations remain to be elucidated, experimental manipulations suggest that the dysregulations of ER homeostasis that occur due to mutations in TFG lead to neurodegeneration.

KW - Charcot-Marie-Tooth disease

KW - Endoplasmic reticulum

KW - Neurodegeneration

KW - Spastic paraplegia

KW - Tropomyosin-receptor kinase fused gene (TFG)

UR - http://www.scopus.com/inward/record.url?scp=84961943348&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961943348&partnerID=8YFLogxK

U2 - 10.1093/jnen/nlw009

DO - 10.1093/jnen/nlw009

M3 - Article

C2 - 26945032

AN - SCOPUS:84961943348

VL - 75

SP - 299

EP - 305

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 4

ER -