title: Myelin basic protein binds microtubules to a membrane surface and to actin filaments in vitro: effect of phosphorylation and deimination.
abstract: Myelin basic protein (MBP) is a multifunctional protein involved in maintaining the stability and integrity of the myelin sheath by a variety of interactions with membranes and other proteins. It assembles actin filaments and microtubules, can bind actin filaments and SH3-domains to a membrane surface, and may be able to tether them to the oligodendrocyte membrane and participate in signal transduction in oligodendrocytes/myelin. In the present study, we have shown that the 18.5 kDa MBP isoform can also bind microtubules to lipid vesicles in vitro. Phosphorylation of MBP at Thr94 and Thr97 (bovine sequence) by MAPK, and deimination of MBP (using a pseudo-deiminated recombinant form), had little detectable effect on its ability to polymerize and bundle microtubules, in contrast to the effect of these modifications on MBP-mediated assembly of actin. However, these modifications dramatically decreased the ability of MBP to tether microtubules to lipid vesicles. MBP and its phosphorylated and pseudo-deiminated variants were also able to bind microtubules to actin filaments. These results suggest that MBP may be able to tether microtubules to the cytoplasmic surface of the oligodendrocyte membrane, and that this binding can be regulated by post-translational modifications to MBP. We further show that MBP appears to be co-localized with actin filaments and microtubules in cultured oligodendrocytes, and also at the interface between actin filaments at the leading edge of membrane processes and microtubules behind them. Thus, MBP may also cross-link microtubules to actin filaments in vivo.
authors.affiliation: Molecular Structure and Function Program, Research Institute, the Hospital for Sick Children, Toronto, ON, Canada. jmboggs@sickkids.ca
authors.forename: Joan M
authors.initials: JM
authors.lastname: Boggs
authors.forename: Godha
authors.initials: G
authors.lastname: Rangaraj
authors.forename: Yew-Meng
authors.initials: YM
authors.lastname: Heng
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Liu
authors.forename: George
authors.initials: G
authors.lastname: Harauz
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D007097:Imines / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D007097:Imines; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D014404:Tubulin