title: Peripheral myelin protein 22 kDa and protein zero: domain specific trans-interactions.
abstract: The peripheral myelin proteins P0 and PMP22 are associated in preparations of compact myelin and in cell cultures coexpressing both molecules. The mechanism of this interaction, however, still needs to be unravelled. We have established three different (cell-cell, cell-protein, protein-protein based) assay systems using retrovirally transduced HeLa cells that overexpressed either PMP22 or P0 and purified GST fusion oligopeptides of PMP22 and P0 to detect domain-specific interactions between these proteins. The results revealed that PMP22 and P0 are involved in both trans-homophilic and trans-heterophilic interactions. Moreover, the data clearly indicate that the heterophilic trans-interaction is mediated through the second loop of PMP22, while the first loop is involved in homophilic trans-interaction of PMP22 proteins. Both modes of interaction are due to direct protein-protein binding. In addition, we demonstrate that disease-related point mutations of P0 resulted in a decreased adhesion capability correlating with the severity of the respective disease phenotype.
authors.affiliation: Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hasse
authors.forename: Frank
authors.initials: F
authors.lastname: Bosse
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Müller
mesh_terms: D001681:Biological Assay / Q000379:methods; D002448:Cell Adhesion / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008967:Molecular Biology / Q000379:methods; D009154:Mutation / Q000235:genetics; D018993:Myelin P0 Protein / Q000737:chemistry / Q000235:genetics*; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics*; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism* / Q000503:physiopathology; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins; D014161:Transduction, Genetic
chemical_list: D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human; D011993:Recombinant Fusion Proteins