Analysis of peripheral nerve expression profiles identifies a novel myelin glycoprotein, MP11.
The myelin sheath insulates axons and allows for rapid salutatory conduction in the nervous system of all vertebrates. The formation of peripheral myelin requires expression of the transcription factor Egr2, which is responsible for inducing such essential myelin-associated genes as Mpz, Mbp, Pmp22, and Mag. Using microarray analysis to compare gene expression patterns in peripheral nerve during development, during remyelination after nerve injury, and in a congenital hypomyelinating mouse model, we identified an evolutionarily conserved novel component of myelin called Mp11 (myelin protein of 11 kDa). The Mp11 genomic locus contains multiple conserved Egr binding sites, and Mp11 induction is regulated by the expression of Egr2. Similar to other Egr2-dependent genes, it is induced during developmental myelination and remyelination after nerve injury. Mp11 is a glycoprotein expressed preferentially in the myelin of the peripheral nervous system versus CNS and is specifically localized to the Schmidt-Lanterman incisures and paranodes of peripheral nerve. The Mp11 protein contains no identifiable similarity to other known protein domains or motifs. However, like other myelin genes, strict Mp11 expression levels are a requirement for the in vitro myelination of DRG neurons, indicating that this previously uncharacterized gene product is a critical component of peripheral nervous system myelin.
Ryu
Elizabeth J
EJ
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Yang
Mao
M
Gustin
Jason A
JA
Chang
Li-Wei
LW
Freimuth
Robert R
RR
Nagarajan
Rakesh
R
Milbrandt
Jeffrey
J
D000818:Animals; D002478:Cells, Cultured; D051767:Early Growth Response Protein 2 / Q000502:physiology; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D012584:Sciatic Nerve / Q000254:growth & development / Q000293:injuries / Q000378:metabolism*; D016415:Sequence Alignment / Q000379:methods; D014162:Transfection / Q000379:methods
D051767:Early Growth Response Protein 2; C497328:Egr2 protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; C530917:NCMAP protein, human; C530918:Ncmap protein, mouse; C530916:Ncmap protein, rat