Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom

Berger, Philipp; Sirkowski, Erich; Scherer, Steven S.; Suter, Ueli

doi:10.1016/j.nbd.2004.07.014

Cited by 46 publications

(52 citation statements)

References 49 publications

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“…Although the inconsistency may be caused by the difference in animal species or developmental process, the possibility of unexpected cross-reactions of their antibody to other NDRGs (probably NDRG2) cannot be ruled out. In fact, our observation of NDRG1 localization in oligodendrocytes is consistent with that of another report (Berger et al 2004).…”

Section: Discussionsupporting

confidence: 93%

Differential Expression Patterns of NDRG Family Proteins in the Central Nervous System

Okuda

Kokame

Miyata

2007

J Histochem Cytochem.

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S U M M A R Y The N-myc downstream-regulated gene (NDRG) family consists of four proteins: NDRG1, NDRG2, NDRG3, and NDRG4 in mammals. NDRG1 has been thoroughly studied as an intracellular protein associated with stress response, cell growth, and differentiation. A nonsense mutation in the NDRG1 gene causes hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D. We previously generated Ndrg1-deficient mice and found that they exhibited peripheral nerve degeneration caused by severe demyelination, but that the complicated motor abilities were retained. These results implied that other NDRG family proteins may compensate for the NDRG1 deficiency in the central nervous system. In this study we raised specific antibodies against each member of the NDRG protein family and examined their cellular expression patterns in the mouse brain. In the cerebrum, NDRG1 and NDRG2 were localized in oligodendrocytes and astrocytes, respectively, whereas NDRG3 and NDRG4 were ubiquitous. In the cerebellum, NDRG1 and NDRG4 were localized in Purkinje cells and NDRG2 in Bergmann glial cells. NDRG3 was detected in the nuclei in most cells. These expression patterns demonstrated the cell type-specific and ubiquitous localization of the NDRG family proteins. Each NDRG may play a partially redundant role in specific cells in the brain. (J Histochem Cytochem 56:175-182, 2008)

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Section: Discussionsupporting

confidence: 93%

Differential Expression Patterns of NDRG Family Proteins in the Central Nervous System

Okuda

Kokame

Miyata

2007

J Histochem Cytochem.

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“…We show that in rodent oligodendrocytes, which normally exhibit strong Ndrg1 expression in the cytoplasm and processes (Berger et al, 2004;Okuda et al, 2008), Ndrg1 deficiency results in reduced LDL uptake. Importantly, this implies that the NDRG1 effect on LDL uptake is not specific for a certain cell type or species.…”

Section: Ndrg1 and Cmt4dmentioning

confidence: 75%

NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation

Pietiäinen

Vassilev

Blom

et al. 2013

Journal of Cell Science

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Summary N-myc downstream-regulated gene 1 (NDRG1) mutations cause Charcot-Marie-Tooth disease type 4D (CMT4D). However, the cellular function of NDRG1 and how it causes CMT4D are poorly understood. We report that NDRG1 silencing in epithelial cells results in decreased uptake of low-density lipoprotein (LDL) due to reduced LDL receptor (LDLR) abundance at the plasma membrane. This is accompanied by the accumulation of LDLR in enlarged EEA1-positive endosomes that contain numerous intraluminal vesicles and sequester ceramide. Concomitantly, LDLR ubiquitylation is increased but its degradation is reduced and ESCRT (endosomal sorting complex required for transport) proteins are downregulated. Co-depletion of IDOL (inducible degrader of the LDLR), which ubiquitylates the LDLR and promotes its degradation, rescues plasma membrane LDLR levels and LDL uptake. In murine oligodendrocytes, Ndrg1 silencing not only results in reduced LDL uptake but also in downregulation of the oligodendrocyte differentiation factor Olig2. Both phenotypes are rescued by co-silencing of Idol, suggesting that ligand uptake through LDLR family members controls oligodendrocyte differentiation. These findings identify NDRG1 as a novel regulator of multivesicular body formation and endosomal LDLR trafficking. The deficiency of functional NDRG1 in CMT4D might impair lipid processing and differentiation of myelinating cells.

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“…3 and 4). NDRG1, a cytoplasmic protein that is expressed by OLs (29) and validated by immunoblotting in human myelin (Fig. 4), has been identified as a Rab4a effector recruited to recycling/sorting endosomes in cell lines (30).…”

Section: Protein Identification By Sequential 1-dimensional Page and mentioning

confidence: 98%

Human myelin proteome and comparative analysis with mouse myelin

Ishii¹,

Dutta

Wark³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

103

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Myelin, formed by oligodendrocytes (OLs) in the CNS, is critical for axonal functions, and its damage leads to debilitating neurological disorders such as multiple sclerosis. Understanding the molecular mechanisms of myelination and the pathogenesis of human myelin disease has been limited partly by the relative lack of identification and functional characterization of the repertoire of human myelin proteins. Here, we present a large-scale analysis of the myelin proteome, using the shotgun approach of 1-dimensional PAGE and liquid chromatography/tandem MS. Three hundred eight proteins were commonly identified from human and mouse myelin fractions. Comparative microarray analysis of human white and gray matter showed that transcripts of several of these were elevated in OL-rich white matter compared with gray matter, providing confidence in their detection in myelin. Comparison with other databases showed that 111 of the identified proteins/transcripts also were expressed in OLs, rather than in astrocytes or neurons. Comparison with 4 previous myelin proteomes further confirmed more than 50% of the identified proteins and revealed the presence of 163 additional proteins. A select group of identified proteins also were verified by immunoblotting. We classified the identified proteins into biological subgroups and discussed their relevance in myelin biogenesis and maintenance. Taken together, the study provides insights into the complexity of this metabolically active membrane and creates a valuable resource for future in-depth study of specific proteins in myelin with relevance to human demyelinating diseases.microarray ͉ oligodendrocyte ͉ proteomics ͉ mass spectrometry

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Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom

Cited by 46 publications

References 49 publications

Differential Expression Patterns of NDRG Family Proteins in the Central Nervous System

Differential Expression Patterns of NDRG Family Proteins in the Central Nervous System

NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation

Human myelin proteome and comparative analysis with mouse myelin

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