Neurochemical Research

, Volume 32, Issue 2, pp 137–158

A Tale of Two Citrullines—Structural and Functional Aspects of Myelin Basic Protein Deimination in Health and Disease

Original Paper

DOI: 10.1007/s11064-006-9108-9

Cite this article as:
Harauz, G. & Musse, A.A. Neurochem Res (2007) 32: 137. doi:10.1007/s11064-006-9108-9

Abstract

Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.

Keywords

Citrulline Deimination Peptidylarginine deiminase Multiple sclerosis Myelin Myelin basic protein Rheumatoid arthritis 

Abbreviations

ADP

Adenosine diphosphate

BAEE

α-N-benzoyl-l-arginine ethyl ester

C1–C8

MBP charge components 1–8 (h—human, b—bovine, rm—recombinant murine)

CaM

Calmodulin

Cit

Citrulline

Cit-MBP

Citrullinated (deiminated) MBP

CNS

Central nervous system

DAG

Diacylglycerol

EAE

Experimental allergic/autoimmune encephalomyelitis

EPR

Electron paramagnetic resonance

GFAP

Glial fibrillary acidic protein

Golli

Genes of the oligodendrocyte lineage

HPLC

High-performance liquid chromatography

MAP

Microtubule-associated protein

MARCKS

Myristoylated alanine-rich C kinase substrate

MBP

Myelin basic protein (hMBP human, bMBP bovine, mMBP murine, rmMBP recombinant murine)

MOG

Myelin/oligodendrocyte glycoprotein

MS

Multiple sclerosis

NADP+/NADPH

Nicotinamide adenine dinucleotide phosphate (oxidised/reduced)

PAD

Peptidylarginine deiminase, EC 3.5.3.15

PAGE

Polyacrylamide gel electrophoresis

PI

Phosphatidylinositol

PLC

Phospholipase C

PRMT

Protein-Arg-N-methyltransferase

rmC1, rmC8

Recombinant murine analogues of natural C1, C8 isomers

SDS

Sodium dodecyl sulphate

SDSL

Site-directed spin labelling

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Molecular and Cellular Biology, and Biophysics Interdepartmental GroupUniversity of GuelphGuelphCanada