Charcot–Marie–Tooth disease and intracellular traffic

Bucci, Cecilia; Bakke, Oddmund; Progida, Cinzia

doi:10.1016/j.pneurobio.2012.03.003

Cited by 63 publications

(53 citation statements)

References 641 publications

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“…1 , 2 The CMT type 2B (CMT2B) is a dominant axonal form caused by 5 mutations (L129F, K157N, N161T, V162M and the recently identified N161I) in the RAB7A gene, 3–6 and it is characterized by prominent sensory loss, lower legs muscle atrophy, high frequency of foot ulcers and recurrent infections leading to toe amputations. 7–9 …”

Section: Introductionmentioning

confidence: 99%

Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

et al. 2018

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Charcot-Marie-Tooth type 2B (CMT2B) disease is a dominant axonal peripheral neuropathy caused by 5 mutations in the RAB7A gene, a ubiquitously expressed GTPase controlling late endocytic trafficking. In neurons, RAB7A also controls neuronal-specific processes such as NTF (neurotrophin) trafficking and signaling, neurite outgrowth and neuronal migration. Given the involvement of macroautophagy/autophagy in several neurodegenerative diseases and considering that RAB7A is fundamental for autophagosome maturation, we investigated whether CMT2B-causing mutants affect the ability of this gene to regulate autophagy. In HeLa cells, we observed a reduced localization of all CMT2B-causing RAB7A mutants on autophagic compartments. Furthermore, compared to expression of RAB7AWT, expression of these mutants caused a reduced autophagic flux, similar to what happens in cells expressing the dominant negative RAB7AT22N mutant. Consistently, both basal and starvation-induced autophagy were strongly inhibited in skin fibroblasts from a CMT2B patient carrying the RAB7AV162M mutation, suggesting that alteration of the autophagic flux could be responsible for neurodegeneration.

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Section: Introductionmentioning

confidence: 99%

Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

et al. 2018

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“…Damage to intracellular traffic is supposed to be one of the most important factors leading to different neuronal diseases, among them distal hereditary motor neuropathy and/or Charcot-Marie-Tooth disease (Bucci et al 2012). The system of intermediate filaments plays an important role in the intracellular traffic .…”

Section: Discussionmentioning

confidence: 99%

“…Light neurofilament (NFL) protein is predominantly responsible for polymerization of intermediate filaments (Heins et al 1993;Lifsics and Williams 1984), whereas two other components predominantly participate in interfilament interaction . Mutations of NFH are associated with amyotrophic lateral sclerosis, whereas mutations of NFL are associated with different forms of Charcot-Marie-Tooth disease (Eriksson et al 2009;Bucci et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Interaction of small heat shock proteins with light component of neurofilaments (NFL)

Nefedova

Sudnitsyna

Gusev

2017

Cell Stress and Chaperones

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The interaction of human small heat shock protein HspB1, its point mutants associated with distal hereditary motor neuropathy, and three other small heat shock proteins (HspB5, HspB6, HspB8) with the light component of neurofilaments (NFL) was analyzed by differential centrifugation, analytical ultracentrifugation, and fluorescent spectroscopy. The wild-type HspB1 decreased the quantity of NFL in pellets obtained after low-and high-speed centrifugation and increased the quantity of NFL remaining in the supernatant after high-speed centrifugation. Part of HspB1 was detected in the pellet of NFL after high-speed centrifugation, and at saturation, 1 mol of HspB1 monomer was bound per 2 mol of NFL. Point mutants of HspB1 associated with distal hereditary motor neuropathy (G84R, L99M, R140G, K141Q, and P182S) were almost as effective as the wild-type HspB1 in modulation of NFL assembly. At low ionic strength, HspB1 weakly interacted with NFL tetramers, and this interaction was increased upon salt-induced polymerization of NFL. HspB1 and HspB5 (αB-crystallin) decreased the rate of NFL polymerization measured by fluorescent spectroscopy. HspB6 (Hsp20) and HspB8 (Hsp22) were less effective than HspB1 (or HspB5) in modulation of NFL assembly. The data presented indicate that the small heat shock proteins affect NFL transition from tetramers to filaments, hydrodynamic properties of filaments, and their bundling and therefore probably modulate the formation of intermediate filament networks in neurons.

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“…Mutations in proteins regulating these transport pathways have been associated with neuronal pathologies [e.g. mental retardation (Borck et al, 2008), Alzheimer's disease (Adachi et al, 2009;Mathews et al, 2002)] and neuro-muscular functions, as seen in Charcot-MarieTooth disease (Bucci et al, 2012), thereby showing their importance for a proper neuronal cell function during development.…”

Section: Introductionmentioning

confidence: 99%

A high throughput siRNA screen identifies genes that regulate mannose 6-phosphate receptor trafficking

Anitei

Ramu

Czupalla

et al. 2014

Journal of Cell Science

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The delivery of newly synthesized soluble lysosomal hydrolases to the endosomal system is essential for lysosome function and cell homeostasis. This process relies on the proper trafficking of the mannose 6-phosphate receptors (MPRs) between the trans-Golgi network (TGN), endosomes and the plasma membrane. Many transmembrane proteins regulating diverse biological processes ranging from virus production to the development of multicellular organisms also use these pathways. To explore how cell signaling modulates MPR trafficking, we used high-throughput RNA interference (RNAi) to target the human kinome and phosphatome. Using high-content image analysis, we identified 127 kinases and phosphatases belonging to different signaling networks that regulate MPR trafficking and/or the dynamic states of the subcellular compartments encountered by the MPRs. Our analysis maps the MPR trafficking pathways based on enzymes regulating phosphatidylinositol phosphate metabolism. Furthermore, it reveals how cell signaling controls the biogenesis of post-Golgi tubular carriers destined to enter the endosomal system through a SRCdependent pathway regulating ARF1 and RAC1 signaling and myosin II activity.

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Charcot–Marie–Tooth disease and intracellular traffic

Abstract: Highlights► Intracellular traffic defects cause important human diseases. ► Mutations causing CMT often alter intracellular trafficking. ► Alterations of intracellular traffic are one of the major causes of CMT neuropathy.

Cited by 63 publications

References 641 publications

Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

Interaction of small heat shock proteins with light component of neurofilaments (NFL)

A high throughput siRNA screen identifies genes that regulate mannose 6-phosphate receptor trafficking

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