Molecular evolution of myelin basic protein, an abundant structural myelin component

Abstract

Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of axons, which evolved in ancient cartilaginous fish. We aim to understand the coevolution of myelin and the major myelin proteins. We found that myelin basic protein (MBP) derived from living cartilaginous fish (sharks and rays) associated with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)-bisphosphate (PIP₂)-binding marker PH-PLCδ1, and that ionomycin-induced PIP₂-hydrolysis led to its cellular redistribution. We identified two paralogous mbp genes in multiple teleost species, consistent with a genome duplication at the root of the teleost clade. Zebrafish mbpb is organized in a complex transcription unit together with the unrelated gene-of-the-oligodendrocyte-lineage (golli) while mbpa does not encode GOLLI. Moreover, the embryonic expression of mbpa and mbpb differed, indicating functional specialization after duplication. However, both mbpa and mbpb-mRNAs were detected in mature oligodendrocytes and Schwann cells, MBPa and MBPb were mass spectrometrically identified in zebrafish myelin, both associated with the plasma membrane via PIP₂, and the ratio of nonsynonymous to synonymous nucleotide-substitution rates (Ka/Ks) was low. Together, this indicates selective pressure to conserve many aspects of the cellular expression and function of MBP across vertebrate species. We propose that the PIP₂-binding function of MBP is evolutionarily old and that its emergence in ancient gnathostomata provided glial cells with the competence to myelinate.

CNS Myelin Wrapping Is Driven by Actin Disassembly

“…Cofilin and gelsolin family members are sequestered by membrane PI(4,5)P2 and kept inactive; release from PI(4,5)P2 enables actin filament severing and disassembly (reviewed by Hilpelä et al, 2004). Intriguingly, MBP binds to PI(4,5)P2 on OL membranes, requiring it for stable attachment to the membrane and maintenance of compact myelin (Nawaz et al, 2009; Nawaz et al, 2013). Thus MBP may regulate actin disassembly by competing with cofilin and gelsolin for binding to membrane PI(4,5)P2.…”

EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia

“…7a). Previous studies25 and the ZFIN database detected expression of mbp by in situ hybridization during early somitogenesis at about 11 hpf (http://zfin.org/cgi-bin/webdriver?MIval=aa-fxfigureview.apg&OID=ZDB-FIG-050630-1515), and exosc8 expression at the 14–19 somite stage around 16 hpf (http://zfin.org/cgi-bin/webdriver?MIval=aa-fxallfigures.apg&OID=ZDB-PUB-040907-1&fxallfig_probe_zdb_id=ZDB-EST-080225-97). We did not study expression of the zebrafish smn1 gene, because in contrast to the human SMN1 zebrafish smn1 is not ARE.…”

Myelin in cartilaginous fish

“…The recent sequencing of the lamprey genome brought into light the presence of MBP-like sequences (Smith et al, 2013). However, we and others had searched within the fully sequenced genomes of lamprey and amphioxus and had not found any true MBP (Nawaz et al, 2013; Werner, 2013). Werner’s explanation is that those MBP sequences are just Golli-MBP, which is not involved in myelin formation (Givogri et al, 2001; Paez et al, 2009).…”

“…The myelin basic proteins (MBP) are a family of alternatively spliced proteins (Campagnoni et al, 1993), that are responsible for the cytoplasmic adhesion of myelin as well as interacting with actin, tubulin, clathrin and negatively charged lipids (Boggs, 2006; Dyer et al, 1994; Nawaz et al, 2013). MBPs are so crucial that they are considered indispensable for CNS myelination: all MBP mutant mouse lines suffer severe hypomyelination in contrast to PLP mutants (Popko et al, 1987; Readhead et al, 1987).…”