title: Myelin basic protein as a "PI(4,5)P2-modulin": a new biological function for a major central nervous system protein.
abstract: The 18.5 kDa isoform of myelin basic protein (MBP) is multifunctional and has previously been shown to have structural and phenomenological similarities with domains of other membrane- and cytoskeleton-associated proteins such as MARCKS (myristoylated alanine-rich C kinase substrate). Here, we have investigated whether 18.5 kDa MBP can sequester phosphatidylinositol-(4,5)-bis-phosphate (PI(4,5)P 2) in membranes, like MARCKS and other "PIPmodulins" do. Using fluorescence-quenching and electron paramagnetic resonance (EPR) spectroscopy, and model membranes containing BODIPY-FL- or proxyl-labeled PI(4,5)P 2, respectively, we have demonstrated that MBP laterally sequesters PI(4,5)P 2. The MBP-PI(4,5)P 2 interactions are electrostatic, partially cholesterol-dependent, and sensitive to phosphorylation, deimination, and Ca (2+)-CaM binding. Confocal microscopy of cultured oligodendrocytes also revealed patched colocalization of MBP and PI(4,5)P 2, indicating the spatial clustering of PI(4,5)P 2 in the plasma membrane. On the basis of these findings as well as the overwhelming convergence of functional properties, modifying enzymes, and interaction partners, we propose that MBP is mechanistically related to GAP-43, MARCKS, and CAP-23. During myelinogenesis, it may mediate calcium and phosphorylation-sensitive plasma membrane availability of PI(4,5)P 2. This regulation of PI(4,5)P 2 availability at the cell cortex may be coupled to the elaboration and outgrowth of the membranous cellular processes by oligodendrocytes.
authors.affiliation: Department of Molecular and Cellular Biology and Biophysics Interdepartmental Group, University of Guelph, 50 Stone Road East, Guelph, Ontario, Canada, N1G 2W1.
authors.forename: Abdiwahab A
authors.initials: AA
authors.lastname: Musse
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.forename: Lopamudra
authors.initials: L
authors.lastname: Homchaudhuri
authors.forename: Joan M
authors.initials: JM
authors.lastname: Boggs
authors.forename: George
authors.initials: G
authors.lastname: Harauz