Myelin management by the 18.5-kDa and 21.5-kDa classic myelin basic protein isoforms
Article first published online: 6 MAR 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 125, Issue 3, pages 334–361, May 2013
How to Cite
J. Neurochem.(2013) 125, 334–361.
- Issue published online: 21 APR 2013
- Article first published online: 6 MAR 2013
- Accepted manuscript online: 11 FEB 2013 02:42AM EST
- Manuscript Revised: 5 FEB 2013
- Manuscript Accepted: 5 FEB 2013
- Manuscript Received: 19 DEC 2012
- intrinsically disordered protein;
- myelin basic protein;
The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly and membrane extension, binding to SH3-domains, participation in Fyn-mediated signaling pathways, sequestration of phosphoinositides, and maintenance of calcium homeostasis. Of the diverse post-translational modifications of this isoform, phosphorylation is the most dynamic, and modulates 18.5-kDa MBP's protein-membrane and protein-protein interactions, indicative of a rich repertoire of functions. In developing and mature myelin, phosphorylation can result in microdomain or even nuclear targeting of the protein, supporting the conclusion that 18.5-kDa MBP has significant roles beyond membrane adhesion. The full-length, early-developmental 21.5-kDa splice isoform is predominantly karyophilic due to a non-traditional P-Y nuclear localization signal, with effects such as promotion of oligodendrocyte proliferation. We discuss in vitro and recent in vivo evidence for multifunctionality of these classic basic proteins of myelin, and argue for a systematic evaluation of the temporal and spatial distributions of these protein isoforms, and their modified variants, during oligodendrocyte differentiation.