The myelin proteolipid protein gene modulates apoptosis in neural and non-neural tissues

Skoff, Robert P.; Bessert, Denise; Cerghet, Mirela; Franklin, Michael J.; Rout, Ujjwal K.; Nave, Klaus‐Armin; Carlock, Leon; Ghandour, Mohamedanwar; Armant, D. Randall

doi:10.1038/sj.cdd.4401498

Cited by 20 publications

(29 citation statements)

References 52 publications

(88 reference statements)

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“…The consensus was that PLP functioned as a structural component of myelin, providing stability and maintaining the compact lamellar structure of myelin. Emerging data demonstrate the importance of PLP expression during early brain development in OPCs and neurons (Timsit et al, 1992;Mallon et al, 2002;Miller et al, 2003), as well as in non-neural cells (Skoff et al, 2004). Moreover, a soma-restricted alternatively spliced isoform of PLP was detected in motor neurons and striated muscle before the onset of myelination (Jacobs et al, 2004).…”

Section: Discussionmentioning

confidence: 93%

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex

2006

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In the mammalian CNS, oligodendrocyte precursor cells (OPCs) express most neurotransmitter receptors, but their function remains unclear. The current studies suggest a physiological role for glutamate (AMPA and/or kainate) receptors in OPC migration. AMPA stimulated ␣ v integrin-mediated OPC migration by increasing both the rate of cell movement and the frequency of Ca 2ϩ transients. A protein complex containing the myelin proteolipid protein (PLP) and ␣ v integrin modulated the AMPA-stimulated migration, and stimulation of OPC AMPA receptors resulted in increased association of the AMPA receptor subunits themselves with the ␣ v integrin/PLP complex. Thus, after AMPA receptor stimulation, an ␣ v integrin/PLP/neurotransmitter receptor protein complex forms that reduces binding to the extracellular matrix and enhances OPC migration. To assess the extent to which PLP was involved in the AMPA-stimulated migration, OPCs from the myelin-deficient (MD) rat, which has a PLP gene mutation, were analyzed. OPCs from the MD rat had a normal basal migration rate, but AMPA did not stimulate the migration of these cells, suggesting that the PLP/␣ v integrin complex was important for the AMPA-mediated induction. AMPA-induced modulation of OPC migration was abolished by pertussis toxin, although baseline migration was normal. Thus, G-protein-dependent signaling is crucial for AMPA-stimulated migration of OPCs but not for basal OPC migration. Other signaling pathways involved in this AMPA-stimulated OPC migration were also determined. These studies highlight novel signaling determinants of OPC migration and suggest that glutamate could play a pivotal role in regulating integrin-mediated OPC migration.

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Section: Discussionmentioning

confidence: 93%

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex

2006

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“…B. Werner et al, 2007) The plp/DM20 locus also encodes the more ancient DM20 isoform that lacks a 35 amino acid cytoplasmic loop. DM20 transcripts are detected in the blastocyst (Skoff et al, 2004), seminiferous tubules, myocardial cells, thymus, and spleen (Campagnoni et al, 1992;Pribyl et al, 1996). In the mouse nervous system, DM20 is expressed in neural progenitors as early as embryonic day 9.5 (E9.5) and in oligodendrocyte progenitors by E14.5 (Timsit et al, 1992(Timsit et al, , 1995Yu et al, 1994;Fanarraga et al, 1996;Dickinson et al, 1997;Spassky et al, 1998;Gudz et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Tuason¹,

Rastikerdar²,

Kuhlmann³

et al. 2008

Journal of Neuroscience

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The gene encoding DM20 emerged in cartilaginous fish, descending from a bilaterian ancestor of the M6 proteolipid gene family. Its proteolipid protein (PLP) isoform appeared in amphibians, contains an additional 35 amino acids, and, in the mammalian CNS, is the dominant myelin protein in which it confers an essential neuroprotective function. During development, the DM20 isoform is prominent in a number of tissues, and plp/DM20 transcripts are detected in multiple progenitor populations, including those that continue to express plp/DM20 as they differentiate into myelinating oligodendrocytes. The locus also encodes isoforms with extended leader sequences that accumulate in the cell bodies of several types of neurons. Here, to locate and characterize regulatory sequences controlling the complex plp/DM20 transcription program, putative regulatory sequences, suggested by interspecies conservation, were ligated individually to a minimally promoted eGFPlacZ reporter gene. These constructs were inserted in single copy at a common site adjacent to the hypoxanthine-guanine phosphoribosyltransferase locus in embryonic stem cells and their in vivo expression programs were compared in transgenic mice. Most expressed developmental and cell-specific subprograms accommodated within the known expression phenotype of the endogenous plp/DM20 locus, thus defining multiple components of the combinatorial mechanism controlling its normal temporal and cell-specific program. Along with previously characterized nervous system enhancers, those described here should help expose the content and configuration of elements that are operational in multiple glial and neuronal lineages. The transgenic lines derived here also provide effective markers for multiple stages of glial and neuronal lineage progression.

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“…Alternative splicing of the proteolipid protein (PLP) gene encodes two main ‘classic’ protein isoforms, PLP and DM20, constituents in myelin membrane of oligodendroglia that may have additional functions suggested by localization in neural precursors [1,2], myocardium, spermatozoa, and thymus [3,4,5,6,7]. In mice, alternative splicing of the cryptic 1.1 exon of the PLP gene also encodes two ‘soma-restricted’ protein isoforms, sr-PLP and sr-DM20, expressed by both neurons and oligodendroglia and associated with trafficking/recycling of endocytotic vesicles [8,9,10,11].…”

Section: Introductionmentioning

confidence: 99%

Developmental Activation of the Proteolipid Protein Promoter Transgene in Neuronal and Oligodendroglial Cells of Neostriatum in Mice

Fulton

Paez²,

Spreur³

et al. 2011

Dev Neurosci

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Prior studies suggest that non-canonical proteolipid protein (PLP) gene expression occurs during development in non-myelinating neurons as well as myelinating oligodendroglia in mammalian brain. To assess this possibility in neostriatum, a region of uncertain PLP gene expression in neurons, morphological and electrophysiological tools were used to determine phenotypes of cells with activation of a PLP promoter transgene during the early postnatal period in mice. PLP gene expression is evident in both neuronal and oligodendroglial phenotypes in developing neostriatum, a conclusion based on three novel observations: (1) An enhanced green fluorescent protein (EGFP) reporter of PLP promoter activation was localized in two distinct populations of cells, which exhibit collective, developmental differences of morphological and electrophysiological characteristics in accord with neuronal and oligodendroglial phenotypes of neostriatal cells found during the early postnatal period in both transgenic and wild-type mice. (2) The EGFP reporter of PLP promoter activation was appropriately positioned to serve as a regulator of PLP gene expression. It colocalized with native PLP proteins in both neuronal and oligodendroglial phenotypes; however, only soma-restricted PLP protein isoforms were found in the neuronal phenotype, while classic and soma-restricted PLP protein isoforms were found in the oligodendroglial phenotype. (3) As shown by EGFP reporter, PLP promoter activation was placed to regulate PLP gene expression in only one neuronal phenotype among the several that constitute neostriatum. It was localized in medium spiny neurons, but not large aspiny neurons. These outcomes have significant implications for the non-canonical functional roles of PLP gene expression in addition to myelinogenesis in mammalian brain, and are consistent with potentially independent pathologic loci in neurons during the course of human mutational disorders of PLP gene expression.

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The myelin proteolipid protein gene modulates apoptosis in neural and non-neural tissues

Cited by 20 publications

References 52 publications

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Developmental Activation of the Proteolipid Protein Promoter Transgene in Neuronal and Oligodendroglial Cells of Neostriatum in Mice

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The myelin proteolipid protein gene modulates apoptosis in neural and non-neural tissues

Cited by 20 publications

References 52 publications

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an αvIntegrin/Myelin Proteolipid Protein Complex

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an αvIntegrin/Myelin Proteolipid Protein Complex

Separate Proteolipid Protein/DM20 Enhancers Serve Different Lineages and Stages of Development

Developmental Activation of the Proteolipid Protein Promoter Transgene in Neuronal and Oligodendroglial Cells of Neostriatum in Mice

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Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex

Glutamate Stimulates Oligodendrocyte Progenitor Migration Mediated via an α_vIntegrin/Myelin Proteolipid Protein Complex