Disease relevance of Pmp22

• Point mutations of these proteins and over or under expression of PASII/PMP22 cause various hereditary peripheral neuropathies [1].
• When dorsal root ganglion (DRG) neurons were cocultured on PASII/PMP22 expressing cells, both neurite extension and branching of DRG neurons were significantly inhibited [1].
• The -8.5 kb rPmp22/CAT/lacZ transgene responds to loss of axonal signals during Wallerian degeneration but unlike the endogenous Pmp22 gene, the transgene fails to respond to axonal signals during nerve regeneration after a sciatic nerve crush injury [2].
• Overexpression of PMP22 is responsible for the most common form of inherited neuropathy, Charcot-Marie-Tooth disease (CMT) type 1A [3].
• Rat Schwann cell cultures were stably infected with recombinant retrovirus vectors harboring the rat PMP22 cDNA in sense or antisense orientation [4].

High impact information on Pmp22

• Migratory effector cells downregulate activation markers (CD25, OX-40) but upregulate several chemokine receptors and adsorb MHC class II on their membranes [5].
• CD25-derived peptides function as ergotopes that can be recognized by the antiergotypic T cells [6].
• Thus, CD25 DNA vaccination may induce protection from autoimmunity by inducing a cytokine shift in both the antiergotypic response and the response to the antigens targeted in the disease [6].
• Membrane insertion of PMP 22 was demonstrated by protease treatment of peroxisomes in the absence and presence of detergent [7].
• Characterization of a novel peripheral nervous system myelin protein (PMP-22/SR13) [8].

Biological context of Pmp22

• Our data indicate that axons regulate expression of the CD25 mRNA in Schwann cells, and suggest that the CD25 protein functions during Schwann cell growth and differentiation [9].
• The open reading frame of the CD25 transcript predicts a 17 kDa protein with four putative transmembrane regions [9].
• Furthermore, our findings could provide an explanation for certain phenotypes of PMP22 neuropathy mice that cannot be accounted for by dysmyelination [10].
• Regional localization of rat peripheral myelin protein 22 (Pmp22) gene to chromosome 10q22 by FISH [11].
• Recent expression studies suggest a role of P0 and PMP22 not only in myelination but also during embryonic development [12].

Anatomical context of Pmp22

• 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)] [13].
• Steady-state levels of the CD25 mRNA are very much higher in sciatic nerve than in other tissues, and expression in sciatic nerve is confined to Schwann cells [9].
• Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia [10].
• PMP22 expression is highest in myelinating Schwann cells of peripheral nerves; however, significant levels of PMP22 mRNAs can be detected in a variety of non-neural tissue, including epithelia [10].
• However, PMP22 could only be detected in the SC plasma membrane after basal lamina formation [14].

Associations of Pmp22 with chemical compounds

• The synthesis of glycoprotein Po and peripheral myelin protein 22 in sciatic nerve of male rats is modulated by testosterone metabolites [15].
• This concept is based on the findings that: (a) only 3alpha-diol, which is able to interact with GABAA receptor, is effective in stimulating the synthesis of PMP22 in the sciatic nerve of castrated male rats, and (b) flutamide treatment is ineffective in decreasing the protein levels in intact male rats [15].
• Exogenous expression of PASII/PMP22 in C6 cells significantly inhibited BrdU incorporation to the cells [1].
• Approximately 35% of total in vitro translated PMP 22 became protease resistant after a 1-h incubation at 26 degrees C. Import was dependent on time and temperature, did not require ATP or GTP and was not inhibited by N-ethylmaleimide treatment of neither the soluble components of the translation mixture nor of the isolated peroxisomes [7].
• Role of the peripheral myelin protein 22 N-linked glycan in oligomer stability [16].

Regulatory relationships of Pmp22

• 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 [12].

Other interactions of Pmp22

• For this reason, we currently do not have any functional data supporting that PASII/PMP22 is the member of claudin superfamily [1].
• On the basis of the observations obtained in the Schwann cells cultures, we suggest that the stimulatory effect of neuroactive steroids on Po is acting through PR, while that on PMP22 needs the GABA(A) receptor [17].
• The subcellular localization of PMP22 in cultured brain endothelia was confirmed by internalization with ZO-1 after EGTA-induced disruption of cell junctions [18].
• Prior to the maturation of the BNB and BBB and detection of the tight junction protein occludin, PMP22 is present at ZO-1 positive endothelial junctions of the sciatic nerve and brain cortex [18].
• The resulting SpL201 cell line expresses p75 and nestin, two proteins expressed by neural crest-derived cells, as well as peripheral myelin protein 22, protein zero, and Oct-6 as markers of the Schwann cell lineage [19].

Analytical, diagnostic and therapeutic context of Pmp22

• Low levels of PMP22 were found in early, anti-MAG and anti-GalC immunoreactive, myelinating cocultures [14].
• We here demonstrate that the removal of circulating androgens by orchidectomy induces a significant decrease of the synthesis of Po and PMP22 in the rat sciatic nerve [15].
• (3) We further investigated the expression of PMP22 mRNA by Northern blot in cultured Schwann cells maintained under different conditions of cell growth and arrest [20].
• The data obtained indicate that tetrahydroprogesterone is able to stimulate the gene expression of peripheral myelin protein 22 both in vivo (in adult but not in old animals) and in Schwann cell cultures [21].
• DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response [6].

References