Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro
| Autor: | Joan M. Boggs, Wen Gao, Godha Rangaraj, Yew-Meng Heng |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Static Electricity
Arp2/3 complex macromolecular substances Biochemistry Dephosphorylation Membrane Lipids Microscopy Electron Transmission medicine Animals Humans Protein Isoforms Actin-binding protein Phosphorylation Protein kinase A Cells Cultured Microscopy Confocal biology Chemistry Microfilament Proteins Actin remodeling Myelin Basic Protein Oligodendrocyte Actins Cell biology Myelin basic protein Rats Molecular Weight Oligodendroglia medicine.anatomical_structure biology.protein Cattle Mitogen-Activated Protein Kinases Protein Binding |
| Zdroj: | Biochemistry. 45(2) |
| ISSN: | 0006-2960 |
| Popis: | Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is most likely responsible for adhesion of these surfaces in the multilayered myelin sheath. It can also polymerize actin, bundle F-actin filaments, and bind actin filaments to lipid bilayers through electrostatic interactions. MBP consists of a number of posttranslationally modified isomers of varying charge, some resulting from phosphorylation at several sites by different kinases, including mitogen-activated protein kinase (MAPK). Phosphorylation of MBP in oligodendrocytes occurs in response to various extracellular stimuli. Phosphorylation/dephosphorylation of MBP also occurs in the myelin sheath in response to electrical activity in the brain. Here we investigate the effect of phosphorylation of MBP on its interaction with actin in vitro by phosphorylating the most highly charged unmodified isomer, C1, at two sites with MAPK. Phosphorylation decreased the ability of MBP to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the MBP-actin complex or on the ability of Ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the MBP-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The effect was much greater than that reported earlier for another charge isomer of MBP, C8, in which six arginines were deiminated to citrulline, resulting in a reduction of net positive charge of 6. These results indicate that although average electrostatic forces are the primary determinant of the interaction of MBP with actin, phosphorylation may have an additional effect due to a site-specific electrostatic effect or to a conformational change. Thus, phosphorylation of MBP, which occurs in response to various extracellular signals in both myelin and oligodendrocytes, attenuates the ability of MBP to polymerize and bundle actin and to bind it to a negatively charged membrane. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|