Embryonic Expression of the Soma-Restricted Products of the Myelin Proteolipid Gene in Motor Neurons and Muscle

Developmental Biology Group, Neuropsychiatric Research Institute, Room 47-444, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, California 90024, USA.
Neurochemical Research (Impact Factor: 2.59). 06/2004; 29(5):997-1002. DOI: 10.1023/B:NERE.0000021244.38279.c4
Source: PubMed


In addition to classic proteolipid protein (PLP) and DM20, the mouse myelin proteolipid gene produces the sr-PLP and sr-DM20 proteins. The sr-isoforms are localized to the cell bodies of both oligodendrocytes and neurons. However, they are expressed to a greater extent in neurons than they are in glia. In this study, we examined expression of the sr-proteolipids in the mouse embryo using immunohistochemistry with an sr-PLP/DM20 specific antibody. Widespread expression of the sr-proteins was found in many nonmyelinating cell types. In particular, strong immunoreactivity was detected in motor neurons of both the autonomic and somatic nervous systems as well as in striated muscle. This pattern of expression persisted throughout the embryonic period studied. Thus, the sr-proteolipids are expressed prior to the onset of myelination and in a much broader array of cell types than their classic counterparts. These results support the conclusion that the sr-isoforms of the PLP gene have a biological role independent of myelination.

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Available from: Ernesto R. Bongarzone, Jul 25, 2014
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    • "PLP and DM20 are however known to be differentially expressed both during development and within different regions of the nervous system [10]. DM20, ubiquitously present both in the myelinating Schwann cells and in non-myelinating cells, is the predominant product during embryonic stages of development [11,12], but is overtaken postnatally by PLP which is abundantly expressed in oligodendrocytes and accounts for 17% of the total myelin protein [13]. The amino acid sequence of PLP has been highly conserved during mammalian evolution, with human, mouse and rat PLP sequences being completely homologous to each other [14]. "
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    ABSTRACT: The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP). PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20% of patients. Forty-eight male patients from 38 unrelated families with a PLP1-related disorder were studied. All DNA samples were screened for PLP1 gene duplications using real-time PCR. PLP1 gene sequencing analysis was performed on patients negative for the duplication. The mutational status of all 14 potential carrier mothers of the familial PLP1 gene mutation was determined as well as 15/24 potential carrier mothers of the PLP1 duplication. PLP1 gene duplications were identified in 24 of the unrelated patients whereas a variety of intragenic PLP1 mutations were found in the remaining 14 patients. Of the 14 different intragenic lesions, 11 were novel; these included one nonsense and 7 missense mutations, a 657-bp deletion, a microdeletion and a microduplication. The functional significance of the novel PLP1 missense mutations, all occurring at evolutionarily conserved residues, was analysed by the MutPred tool whereas their potential effect on splicing was ascertained using the Skippy algorithm and a neural network. Although MutPred predicted that all 7 novel missense mutations would be likely to be deleterious, in silico analysis indicated that four of them (p.Leu146Val, p.Leu159Pro, p.Thr230Ile, p.Ala247Asp) might cause exon skipping by altering exonic splicing elements. These predictions were then investigated in vitro for both p.Leu146Val and p.Thr230Ile by means of RNA or minigene studies and were subsequently confirmed in the case of p.Leu146Val. Peripheral neuropathy was noted in four patients harbouring intragenic mutations that altered RNA processing, but was absent from all PLP1-duplication patients. Unprecedentedly, family studies revealed the de novo occurrence of the PLP1 duplication at a frequency of 20%.
    Orphanet Journal of Rare Diseases 06/2011; 6(1):40. DOI:10.1186/1750-1172-6-40 · 3.36 Impact Factor
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    • "Nonetheless, the identification of DM20 in non-myelinating cells suggests an alternative function for the protein in these cells (Campagnoni et al., 1992; Pribyl et al., 1996a, 1996b; Feng et al., 2003; Skoff et al., 2004a). Apart from its expression in mature OLs, the gene encoding PLP is also expressed in OPCs (Gudz et al., 2006), neurons (Bongarzone et al., 1999; Jacobs et al., 2003, 2004; Miller et al., 2003, 2009), embryonic neural precursors (Spassky et al., 1998; Delaunay et al., 2009) and non-neural cells (Campagnoni et al., 1992; Skoff et al., 2004a). The presence of PLP proteins in non-myelinating cells suggests an involvement in other functions unrelated to myelination. "
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    ABSTRACT: It has become clear that the products of several of the earliest identified myelin protein genes perform functions that extend beyond the myelin sheath. Interestingly, these myelin proteins, which comprise proteolipid protein, 2′,3′-cyclic nucleotide 3′-phosphodiesterase and the classic and golli MBPs (myelin basic proteins), play important roles during different stages of oligodendroglial development. These non-myelin-related functions are varied and include roles in the regulation of process outgrowth, migration, RNA transport, oligodendrocyte survival and ion channel modulation. However, despite the wide variety of cellular functions performed by the different myelin genes, the route by which they achieve these many functions seems to converge upon a common mechanism involving Ca2+ regulation, cytoskeletal rearrangements and signal transduction. In the present review, the newly emerging functions of these myelin proteins will be described, and these will then be discussed in the context of their contribution to oligodendroglial development.
    ASN Neuro 01/2010; 2(1). DOI:10.1042/AN20090051 · 4.02 Impact Factor
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    • "The major transcript of this gene in the CNS is proteolipid protein, a lipophilic protein which is the principal component of compact myelin and has non-structural functions in the cell, for PLP has also been found to be a component of membrane complexes involving ␣ v integrin in the oligodendrocyte (Gudz et al., 2002). In addition to Plp expression in oligodendrocytes, our recent studies and those of others have verified the presence of PLP mRNA and protein in neurons in the CNS, including the caudal medulla of the developing rodent (Bongarzone et al., 1999; Jacobs et al., 2003, 2004; Miller et al., 2003, 2009; Greenfield et al., 2006). Because we have documented Plp promoter, Plp mRNA and PLP protein expression in the caudal medulla we hypothesized that this gene could play a heretofore unknown functional role in neurons in this area. "
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    ABSTRACT: Proteolipid protein (Plp) gene mutation in rodents causes severe CNS dysmyelination, early death, and lethal hypoxic ventilatory depression (Miller et al., 2004). To determine if Plp mutation alters neuronal function critical for control of breathing, the nucleus tractus solitarii (nTS) of four rodent strains were studied: myelin deficient rats (MD), myelin synthesis deficient (Plp(msd)), and Plp(null) mice, as well as shiverer (Mbp(shi)) mice, a myelin basic protein mutant. Current-voltage relationships were analyzed using whole-cell patch-clamp in 300 microm brainstem slices. Voltage steps were applied, and inward and outward currents quantified. MD, Plp(msd), and Plp(null), but not Mbp(shi) neurons exhibited reduced outward current in nTS at P21. Apamin blockade of SK calcium-dependent currents and iberiotoxin blockade of BK calcium-dependent currents in the P21 MD rat demonstrated reduced outward current due to dysfunction of these channels. These results provide evidence that Plp mutation specifically alters neuronal excitability through calcium-dependent potassium channels in nTS.
    Respiratory Physiology & Neurobiology 10/2009; 169(3):303-14. DOI:10.1016/j.resp.2009.09.013 · 1.97 Impact Factor
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