2014
Volume 14, Number 3, pp. 57–63
Different isoforms of deiminated myelin basic protein have different adsorption capacities to the myelin lipids
L.V. Shanshiashvili,1, 2 I.V. Kalandadze,2 J.J. Ramsden3, 4 and D.G. Mikeladze1, 2
1 Ilia State University, 3/5 Cholokhashvili St, 0162 Tbilisi, Georgia
2 I. Beritashvili Centre of Experimental Biomedicine, 14 Gotua St, 0160 Tbilisi, Georgia
3 Collegium Basilea, Institute of Advanced Study, 51 Hochstrasse , 4053 Basel, Switzerland
4 Clore Laboratory, University of Buckingham, MK18 1EG, UK
Myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. MBP has extensive posttranslational modifications, including deimination of arginine residues. The deiminated (citrullinated) MBP C8 isomer is divided into two fractions: stathmin-containing C8a; and C8b. Here, we report our investigation of the adhesion of these component fractions to myelin lipids and our finding that the adsorption–desorption characteristics of C8a and C8b are different. The area on the lipid bilayer that is occupied by C8a is slightly smaller than for C8b and the rate coefficient for the association preceding adhesion is also smaller for C8a than for C8b. Taking into account that stathmin is the main component of C8a it is inferred that the stathmin–MBP complex changes the conformation of citrullinated C8 and depresses its capacity to adsorb. Furthermore, we have determined the production of nitric oxide (NO) by astrocytes and by mixed primary glial cells under the actions of C8a and C8b. We have found that NO synthesis is not changed in astrocytes in the presence of the C8a and C8b fractions, whereas in the primary glia the production of NO is significantly increased. We suggest that this increase is due to the presence of microglia in mixed primary glial cells, which are the primary targets of the various forms of MBP.
Keywords: deimination, glial cells, myelin basic protein, myelination, protein adhesion, stathmin