Myelin proteolipid protein forms a complex with integrins and may participate in integrin receptor signaling in oligodendrocytes.
Myelination of axons in the CNS by oligodendrocytes is a process critical to rapid and efficient impulse conduction. A new role for the myelin proteolipid protein (PLP), the most abundant protein of CNS myelin, has been identified, in studies showing PLP interaction with signaling proteins in oligodendrocytes. In particular, these studies suggest that the PLP protein may be involved in signaling through integrins in oligodendrocytes. Stimulation of muscarinic acetylcholine receptors on oligodendrocytes induced formation of a tripartite complex containing PLP, calreticulin, and alpha(v)-integrin. PLP interacted directly with the cytoplasmic domain of the alpha(v)-integrin. Complex formation was mediated by phospholipase C and Ca2+ binding to the high affinity binding site on calreticulin. This complex appears important for binding of fibronectin to oligodendrocytes. These data establish a novel function for PLP as a part of the integrin signaling complex in oligodendrocytes and suggest that neurotransmitter-mediated integrin receptor signaling may be involved in myelinogenesis.
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Tatyana I
TI
Gudz
Tracy E
TE
Schneider
Thomas A
TA
Haas
Wendy B
WB
Macklin
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D039564:Integrin alphaV; D016023:Integrins / Q000378:metabolism*; D046911:Macromolecular Substances; D018721:Muscarinic Agonists / Q000494:pharmacology; D018991:Myelin Proteolipid Protein / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D039564:Integrin alphaV; D016023:Integrins; D046911:Macromolecular Substances; D018721:Muscarinic Agonists; D018991:Myelin Proteolipid Protein; D011956:Receptors, Cell Surface; D012261:Ribonucleoproteins; D010738:Type C Phospholipases; D002118:Calcium