Disease relevance of Mpz

• In the human carcinoma cell line T47D expressing high levels of PROG receptor, PROG did not stimulate the P0 and PMP22 promoters, whereas the promoter region of the mouse mammary tumor virus was fully activated [1].
• Utilizing a panel of synthetic P0 peptides two distinct T cell epitopes have been identified that can induce T cell-mediated experimental autoimmune neuritis (EAN) in the Lewis rat [2].
• Degradation of the P0, P1, and Pr proteins in peripheral nervous system myelin by plasmin: implications regarding the role of macrophages in demyelinating diseases [3].
• The rat Schwannoma cell line D6P2T constitutively expresses the mRNA encoding the major myelin protein, P0, but only expresses the mRNA encoding myelin basic protein (MBP) after exposure to forskolin or other substances that raise the levels of intracellular cyclic AMP [4].
• The mRNA and protein steady state levels of the myelin specific genes, P0 and the MBPs, decreased to low yet detectable levels during Wallerian degeneration and returned to normal levels with subsequent axonal regeneration [5].

Psychiatry related information on Mpz

• An inverse relationship between Id1/3 and myelin P0 expression was consistent with a role for these two Id proteins as inhibitors of differentiation, and Id1/3 proteins strongly repressed myelin gene promoter activity [6].
• Experiments on discrimination learning show that 10mg/kg of MPP enhance the response decision speed in presence of S(+) (white arm) and S(-) (black arm) [7].

High impact information on Mpz

• Furthermore, we find that the induction of P0 mRNA coincides with the initiation of myelin formation, and we propose a model in which the glycoprotein serves as a molecular guidepost for this process [8].
• The sequence of this protein, deduced from the nucleotide sequence of the cloned cDNA, indicates that P0 is an integral membrane protein containing a single membrane-spanning region, a large hydrophobic extracellular domain, and a smaller basic intracellular domain [8].
• These three glial cells develop in a fixed sequence over a two-week period: type-1 astrocytes appear at embryonic day 16 (E16), oligodendrocytes at the day of birth (E21 or postnatal day P0), and type-2 astrocytes between P8 and P10 [9].
• Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression [10].
• Here, using more detailed measurement of stimulus intensity curves, we report that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h [10].

Chemical compound and disease context of Mpz

• P0 glycoprotein peptides 56-71 and 180-199 dose-dependently induce acute and chronic experimental autoimmune neuritis in Lewis rats associated with epitope spreading [11].
• Expression of major myelin glycoprotein P0 by P0 cDNA transfection into C6 glioma cells promoted homophilic cell adhesion of the cells [12].
• Three cyclic analogs of gamma-aminobutyric acid (GABA)-5-ethyl, 5-phenyl, 2-pyrrolidinone (EPP), 5-diphenyl, 2-pyrrolidinone (DPP), and 5-methyl, 5-phenyl, 2-pyrrolidinone (MPP)- were studied in relation to protein synthesis and the latter in relation to discrimination learning [7].
• The high affinity of suramin for partially purified myelin P0 protein suggests a possible mechanism for drug-induced toxicity [13].
• P0 in the presence of lysophosphatidylcholine induced paralysis and histological lesions resembling experimental allergic neuritis in Lewis rats [14].

Biological context of Mpz

• In contrast to prototypical immunoglobulin domains, however, this P0 domain is encoded by two exons, the partitioning of which provides genetic evidence for the evolution of immunoglobulin-related domains from an ancestral half-domain [15].
• We also describe procedures for transfection of cultures of nontransformed rat Schwann cells and use these procedures to show that the Schwann cell-specific expression of the P0 gene is controlled by cis-acting elements localized upstream of exon I [15].
• In contrast, treatment with THP increased gene expression of P0 exclusively in female Schwann cells [16].
• Recent expression studies suggest a role of P0 and PMP22 not only in myelination but also during embryonic development [17].
• Two amino-acid substitutions in the myelin protein zero gene of a case of Charcot-Marie-Tooth disease associated with light-near dissociation [18].

Anatomical context of Mpz

• Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin [19].
• Here we show that, in dorsal root ganglia (DRG) and differentiated neural crest cultures, P0 is expressed in the glial lineage whereas PMP22 is also detectable in neurons [17].
• In cultures of differentiating neural crest, a similar multipotent cell type can be identified in which expression of P0 and PMP22 precedes the appearance of neural differentiation markers [17].
• Like neural crest stem cells (NCSCs), this P0/PMP22-positive cell gives rise to glia, neurons and smooth-muscle-like cells in response to instructive extracellular cues [17].
• Transection of sciatic nerve in adult rat leads to a simultaneous and rapid decline in both PMP22 and P0 mRNA to nondetectable levels in the degenerating distal stump [20].

Associations of Mpz with chemical compounds

• Data obtained in our and other laboratories have indicated that progesterone (P) and its derivatives, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), stimulate the expression of two myelin proteins of the peripheral nervous system (PNS) [i.e., glycoprotein zero (P0) and peripheral myelin protein 22 (PMP22)] [16].
• In contrast to the transected nerve, addition of NH4Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs [21].
• Alternating 1-micrometer-thick Epon sections were stained with paraphenylenediamine (PD) or with P0 antiserum according to the peroxidase-antiperoxidase method [22].
• The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing [21].
• Our findings suggest that only Schwann cells which have been induced to myelinate make detectable amounts of galactocerebroside (GC), sulfatide, myelin basic protein (BP), or the major peripheral myelin glycoprotein (P0) [23].

Analytical, diagnostic and therapeutic context of Mpz

• The requirements for crystallization of P0ex are similar to those for maintaining the native extracellular spacing of adjacent myelin lamellae; thus, given the self-adhesive character of P0ex, the crystal itself may reveal some of the natural interactions that occur between P0 molecules in myelin [19].
• The distribution of 32P among proteins also differed in diabetic nerve compared with both control groups in that P0 and the small basic protein accounted for a greater proportion of total label incorporated along the entire length of nerve [24].
• In rat cocultures of dorsal root ganglia (DRG) and Schwann cells (SC) grown in serum- and insulin-free defined medium, IGF-I induces a dose dependent upregulation in myelin proteins such as P0, corresponding to maximal SC ensheathment [25].
• To examine further the ability of Schwann cell cultures to express P0 as a function of age, we have performed precursor incorporation studies on endoneurial explants from 4- to 12-day-old rat sciatic nerves after 5 days in culture [26].
• To identify the cysteine residue involved in the thioester linkage, [14C]carboxyamidomethylated P0 was digested with trypsin and the resulting peptides analyzed by reversed-phase HPLC [27].

References