Disease relevance of Plp

• Conduction abnormalities are restricted to the central nervous system in experimental autoimmune encephalomyelitis induced by inoculation with proteolipid protein but not with myelin basic protein [1].
• One week after induction of hydrocephalus, CGa1T and GPCP activity were reduced in the corpus callosum there was less MBP and PLP in the cerebrum, and myelin sheaths around axons greater than 0.4 micron in diameter were abnormally thin [2].
• We assessed the developmental sequence of appearance of CNPase, MBP, MOPB, and PLP proteins in cerebellum (Cb) and corpus callosum (cc) in an experimental hypothyroidism model [3].
• A novel mutation (A246T) in exon 6 of the proteolipid protein gene associated with connatal Pelizaeus-Merzbacher disease [4].
• The number of surviving dorsal root ganglion (DRG) neurons was significantly less than controls when cocultured for 5 d with PLP-expressing cells [5].

High impact information on Plp

• A single amino-terminal methionine is removed post-translationally, indicating that PLP does not require a signal peptide sequence for insertion into the myelin membrane [6].
• The 3200 and 1600 nucleotide mRNAs encoding rat brain proteolipid protein (PLP), the major protein component of central nervous system myelin, are heterogeneous at their 5' ends, differ in their 3' polyadenylation sites, and are transcribed from a single gene [6].
• Nucleotide sequences of two mRNAs for rat brain myelin proteolipid protein [6].
• Relapsing experimental autoimmune encephalomyelitis (R-EAE) induced with the immunodominant epitope from proteolipid protein, PLP139-151, is characterized by the development of recurrent relapses with recruitment of T cells reactive to additional myelin peptides, including PLP178-191 (epitope spreading) [7].
• These observations support the hypothesis that axonal influences affect oligodendrocyte survival, differentiation, and expression of proteolipid protein gene products [8].

Chemical compound and disease context of Plp

• Retinoic acid-regulated expression of proteolipid protein and myelin-associated glycoprotein genes in C6 glioma cells [9].
• Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic acid in C6 glioma cells [10].
• The effect of maternal vitamin B-6 deficiency on concentrations of pyridoxal phosphate (PLP) within four different regions of the central nervous system (CNS) of progeny, the corpus striatum (CS), hypothalamus (H), cerebellum (C), total brain and first cervical segment (C-1) of the spinal cord was determined at 7, 15, 21 and 50 days of age [11].

Biological context of Plp

• We also present evidence that increase in expression of the plp gene along the O-2A lineage differentiation is not progressive but that downregulation at the proligodendroblast (O4+/O1-) stage probably occurs [12].
• Oligonucleotides synthesized according to the established amino-acid sequence of lipophilin and the nucleotide sequence of the small myelin basic protein of the N-terminal, the central and C-terminal region of their sequences were used as hybridization probes for screening [13].
• The largest insert in one of several lipophilin clones was 2,585 base pairs (bp) in length (pLp 1) [13].
• In addition, inspection of the PLP promoter sequence demonstrates the presence of six additional Gtx binding sites [14].
• Immunoprecipitation of labeled DNA fragments encoding either the MBP or PLP promoter regions with this fusion protein has identified several Gtx-binding fragments, and we have confirmed these data using an electrophoretic mobility shift assay [14].

Anatomical context of Plp

• We suggest that progenitors express the dm-20 isoform while oligodendrocytes express predominantly the plp isoform [12].
• In vitro analysis of freshly dissociated cells from premyelinated optic nerve demonstrated that the plp gene is expressed in some O-2A progenitor cells as well as mature oligodendrocytes [12].
• The expression of the lipophilin and myelin basic protein genes during development of the myelin sheath appears to be strictly coordinated [13].
• Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes [15].
• Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes [15].

Associations of Plp with chemical compounds

• Effect of cyclic AMP on the expression of myelin basic protein species and myelin proteolipid protein in committed oligodendrocytes: differential involvement of the transcription factor CREB [16].
• In contrast, almost no changes are observed in myelin proteolipid protein (PLP) or in its mRNA or cholesterol [17].
• Effects of dexamethasone on the expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein genes in developing rat brain [18].
• The threonine to proline mutation located within the second transmembranal alpha-helix might induce a conformational change and thereby prohibit the integration of PLP into the membrane with the clinical manifestation of dysmyelination leading to premature death within 3-6 weeks [19].
• Differential regulation of oligodendrocyte markers by glucocorticoids: post-transcriptional regulation of both proteolipid protein and myelin basic protein and transcriptional regulation of glycerol phosphate dehydrogenase [20].

Regulatory relationships of Plp

• C6 cells expressed less than 0.2% of the proteolipid mRNA that was expressed in primary oligodendrocytes [21].
• Clinical and histological findings in proteolipid protein-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Distribution of demyelination differs from that in EAE induced by other antigens [22].

Other interactions of Plp

• Developmental expression of myelin proteolipid, basic protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase transcripts in different rat brain regions [23].
• In contrast, we have found that db-cAMP stimulates the expression of myelin proteolipid protein (PLP) in a process that occurs despite inhibition of CREB expression [16].
• Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury [24].
• Differentiation did not alter the frequency of association of the PLP gene with domains of myelin transcription factor 1 (Myt1), which binds the PLP promoter [25].
• PLP mRNA-containing oligodendroglia also were more numerous and relative PLP mRNA levels per oligodendrocyte were higher in lesions of IGF-I-treated rats [26].

Analytical, diagnostic and therapeutic context of Plp

• Genomic in situ hybridization was used to detect the single copy of the X-linked PLP gene within each interphase nucleus [25].
• ELISA assays for MBP and PLP antibody showed a similar pattern [27].
• PLP mRNA expression was studied by RT-PCR [28].
• Immunoblotting showed that two integral membrane proteins of myelin, the proteolipid protein (PLP) and the DM-20 protein, were completely extracted under these conditions [29].
• MBP peptide 89-101 and PLP peptide 178-191 induced EAE upon active immunization although proteolipid protein peptide 139-151 was ineffective in this regard [30].

References