Schwann cell caveolin‐1 expression increases during myelination and decreases after axotomy

Mikol, Daniel D.; Scherer, Steven S.; Duckett, Sara J.; Hong, Hoylond L.; Feldman, Eva L.

doi:10.1002/glia.10063

Cited by 46 publications

(44 citation statements)

References 64 publications

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“…It has been noted previously that the abundance of a large number of mRNAs expressed in Schwann cells increases only late after myelination (e.g., genes involved in storage lipid metabolism) (Verheijen et al, 2003). The corresponding cluster (Late-UP) includes fatty acid synthase (Fasn) (Salles et al, 2002), Cdh1, Ndrg1 (Berger et al, 2004), dystrophin-related protein 2 (Drp2), caveolin-1 (Cav1) (Mikol et al, 2002), and the actin filament-severing gelsolin (Gsn) (Gonçalves et al, 2010). There is also a large cluster of mRNAs of which the abundance significantly decreases after the early stages ("descending"), though the protein product has been identified by MS in mature myelin.…”

Section: Abundance Profiles Of Mrnas Encoding Pns Myelin Proteinsmentioning

confidence: 99%

Quantitative and Integrative Proteome Analysis of Peripheral Nerve Myelin Identifies Novel Myelin Proteins and Candidate Neuropathy Loci

Patzig¹,

Jahn²,

Tenzer³

et al. 2011

J. Neurosci.

158

190

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Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions. Many aspects of myelin biogenesis, glia-axonal interactions, and nerve homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far. Combining gel-based and gel-free proteomic approaches, we identified 545 proteins in purified mouse sciatic nerve myelin, including 36 previously known myelin constituents. By mass spectrometric quantification, the predominant P0, periaxin, and myelin basic protein constitute 21, 16, and 8% of the total myelin protein, respectively, suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization. Focusing on tetraspan-transmembrane proteins, we validated novel myelin constituents using immunobased methods. Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation. By differential myelin proteome analysis, we found that the abundance of septin 9, the protein affected in hereditary neuralgic amyotrophy, is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion protein. Finally, the systematic comparison of our compendium with the positions of human disease loci allowed us to identify several candidate genes for hereditary demyelinating neuropathies. These results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin. Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions. Many aspects of myelin biogenesis, glia-axonal interactions, and nerve homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far. Combining gel-based and gel-free proteomic approaches, we identified 545 proteins in purified mouse sciatic nerve myelin, including 36 previously known myelin constituents. By mass spectrometric quantification, the predominant P0, periaxin, and myelin basic protein constitute 21, 16, and 8% of the total myelin protein, respectively, suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization. Focusing on tetraspan-transmembrane proteins, we validated novel myelin constituents using immuno-based methods. Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation. By differential myelin proteome analysis, we found that the abundance of septin 9, the protein affected in hereditary neuralgic amyotrophy, is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion pr...

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Section: Abundance Profiles Of Mrnas Encoding Pns Myelin Proteinsmentioning

confidence: 99%

Quantitative and Integrative Proteome Analysis of Peripheral Nerve Myelin Identifies Novel Myelin Proteins and Candidate Neuropathy Loci

Patzig¹,

Jahn²,

Tenzer³

et al. 2011

J. Neurosci.

158

190

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“…We have demonstrated that RAGE promotes S100B secretion from SC by recruiting S100B in secretory vesicles and that RAGE triggering induces the phosphorylation of caveolin 1 (cav-1), which is necessary for RAGE-promoted S100B secretion and morphological changes in SCs (Perrone et al, 2008). It has been suggested that cav-1 has a function in myelinating SCs (Mikol et al, 2002) and diabetic neuropathy is exacerbated in Cav1 -/-mice (Donato et al, 2009). Cav-1 is associated with membrane microdomains that are enriched in cholesterol and sphingolipids and defined as lipid rafts (Cohen et al, 2004;Perrone and Zurzolo, 2003).…”

Section: Introductionmentioning

confidence: 99%

RAGE–TXNIP axis is required for S100B-promoted Schwann cell migration, fibronectin expression and cytokine secretion

Sbai

Devi

Melone

et al. 2010

Journal of Cell Science

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SummaryDuring peripheral nerve injury, Schwann cells (SCs) adopt a migratory phenotype and remodel the extracellular matrix and provide a supportive activity for neuron regeneration. SCs synthesize neurotrophic factors and cytokines that are crucial for the repair of the injured nerve. The receptor for advanced glycation end products (RAGE) and its ligand S100B, which are secreted by SCs, are required for the repair of the injured peripheral nerve in vivo. However, the precise intracellular pathways involved have not been completely elucidated. Here, we show that RAGE-induced S100B secretion involves the recruitment of S100B in lipid rafts and caveolae. Moreover, we demonstrate for the first time that RAGE induces the expression of thioredoxin interacting protein (TXNIP) in SCs and the injured sciatic nerve in vivo. TXNIP is involved in the activation of p38 MAPK, CREB and NFB in SCs. TXNIP silencing partially inhibits RAGE-induced SC migration and completely abolishes RAGE-induced fibronectin and IL-1 expression. Our results support a model in which TXNIP mediates in part RAGE-induced SC migration and is required for the expression of provisional ECM and pro-inflammatory IL-1. We provide new insight on the role of the SC RAGE-TXNIP axis in the repair of injured peripheral nerves.

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“…Cholesterol comprises about 25% of myelin lipid, and SCs derive all their cholesterol for myelination from de novo synthesis (Jurevics and Morell, 1995). Facilitating cholesterol transport would be consistent with the presence of a cytosolic pool of Cav-1 in SCs (Mikol et al, 1999) and increased Cav-1 expression during periods of active myelination in vivo (Mikol et al, 2002). Furthermore, Cav-1 also strongly colocalizes with staining for myelin basic protein, a marker of myelinating SCs, suggesting a tight association of Cav-1 with myelination ( Fig.…”

Section: Caveolin-1 In Schwann Cell Function and Dpnmentioning

confidence: 77%

“…Similarly, axotomy also strongly down-regulated the expression of Cav-1 in SCs but had little effect on Cav-1 expression in blood vessels or the perineurium (Mikol et al, 2002). These observations suggest that the effect of diabetes on Cav-1 expression may have a very cell-specific basis.…”

Section: Altered Cav-1 Expression In Diabetic Nervementioning

confidence: 79%

“…3). Clearly, the progressive down-regulation of Cav-1 in SCs is a consequence of both metabolic (Tan et al, 2003) and physical (Mikol et al, 2002) insults to peripheral nerve. In vitro data indicate that the gradual loss of Cav-1 expression may remove an inhibitory regulation of endogenous Erb B2 and contribute to an increase in its tyrosine kinase activity.…”

Section: Putative Roles Of Altered Cav-1 Expression In Regulating Erbmentioning

confidence: 99%

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Altered Neurotrophism in Diabetic Neuropathy: Spelunking the Caves of Peripheral Nerve

Dobrowsky

Rouen²,

Yu³

2004

J Pharmacol Exp Ther

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Diabetic peripheral neuropathy (DPN) is a frequent and potentially traumatic complication in diabetic individuals. The chronic nature of diabetes and its associated hyperglycemic episodes initiate a complex and inter-related series of metabolic and vascular insults that contribute to the polygenic etiology of DPN. One contributing factor in DPN is an altered neurotrophism that results from changes in the synthesis and expression of neurotrophins, insulin-like growth factor, and various cytokine-like growth factors that can directly act upon distinct subpopulations of sensory and motor neurons. Although considerable effort has focused upon examining growth factor signaling in hyperglycemically stressed neurons, myelin-forming Schwann cells also undergo substantial degenerative changes in DPN. However, scant attention has been devoted to understanding the effect of hyperglycemia on the response of Schwann cells to growth factors critical to their function. Neuregulins are gliotrophic growth factors that signal through members of the Erb B receptor-tyrosine kinase family. The neuregulin/Erb B ligand-receptor cassette can differentially influence the response of Schwann cells throughout their development by regulating cell survival, mitogenesis, and differentiation. The activity of Erb B receptors may also be affected by their interaction with caveolin-1, a protein marker of caveolae ("little caves"). However, whether neuregulin signaling may be directly or indirectly altered under conditions of hyperglycemic stress and contribute to the physiological progression of DPN is unknown. This brief review will provide a perspective on a putative role of changes in the caveolar proteome of Schwann cells in contributing to an "altered neuregulinism" in DPN.

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Schwann cell caveolin‐1 expression increases during myelination and decreases after axotomy

Cited by 46 publications

References 64 publications

Quantitative and Integrative Proteome Analysis of Peripheral Nerve Myelin Identifies Novel Myelin Proteins and Candidate Neuropathy Loci

Quantitative and Integrative Proteome Analysis of Peripheral Nerve Myelin Identifies Novel Myelin Proteins and Candidate Neuropathy Loci

RAGE–TXNIP axis is required for S100B-promoted Schwann cell migration, fibronectin expression and cytokine secretion

Altered Neurotrophism in Diabetic Neuropathy: Spelunking the Caves of Peripheral Nerve

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