title: Myelin management by the 18.5-kDa and 21.5-kDa classic myelin basic protein isoforms.
abstract: 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.
authors: Department of Molecular and Cellular Biology, Biophysics Interdepartmental Group and Collaborative Program in Neuroscience, University of Guelph, Guelph, Ontario, Canada. gharauz@uoguelph.ca
authors: George
authors: G
authors: Harauz
authors: Joan M
authors: JM
authors: Boggs
mesh_terms: D000818:Animals; D006801:Humans; D008958:Models, Molecular; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains / Q000502:physiology
chemical_list: D004676:Myelin Basic Protein; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn
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