Recombinant peripheral myelin protein P0 confers both adhesion and neurite outgrowth-promoting properties.
To probe into the functional properties of the major peripheral myelin cell surface glycoprotein P0, its ability to confer adhesion and neurite outgrowth-promoting properties was studied in cell culture. To this aim, P0 was expressed as integral membrane glycoprotein at the surface of CV-1 cells with the help of a recombinant vaccinia virus expression system. Furthermore, the immunoglobulin-like extracellular domain of P0 (P0-ED) was expressed as soluble protein in a bacterial expression system and used as substrate coated to plastic dishes or as competitor in cell adhesion and neurite outgrowth-promoting assays. The adhesion of P0-expressing CV-1 cells to P0-ED substrate was specifically inhibitable by polyclonal P0 antibodies (54% +/- 6%). In addition, the specific interaction between P0 molecules could be reduced (49% +/- 8%) by adding soluble P0-ED to the culture medium, demonstrating that the homophilic interaction between recombinant P0 molecules can be mediated, at least on one partner of interacting molecules, by the unglycosylated Ig-like domain. Substrate-coated P0-ED also conferred adhesion and neurite outgrowth ability to dorsal root ganglion neurons with neurites of a mean length of about 150 microns. This neurite outgrowth was specifically inhibitable by soluble P0 (74% +/- 14%) and P0 antibodies (65% +/- 9%). These observations indicate that P0 is capable of displaying two different types of functional roles in the myelination process of peripheral nerves: The heterophilic interaction with neurons may be responsible for the recognition between axon and myelinating Schwann cell at the onset of myelination, whereas the homophilic interaction may indicate its role in the self-recognition of the apposing loops of Schwann cell surface membranes during the myelination process and in the mature compact myelin sheath.
Schneider-Schaulies
J
J
Department of Neurobiology, University of Heidelberg, Federal Republic of Germany.
von Brunn
A
A
Schachner
M
M
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004247:DNA / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology; D005822:Genetic Vectors; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000378:metabolism; D014616:Vaccinia virus
D015816:Cell Adhesion Molecules, Neuronal; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D011994:Recombinant Proteins; D004247:DNA