Secreted glycoprotein myocilin is a component of the myelin sheath in peripheral nerves.
The structure of the myelin sheath in peripheral nerves requires the expression of a specific set of proteins. In the present study, we report that myocilin, a member of the olfactomedin protein family, is a component of the myelin sheath in peripheral nerves. Myocilin is a secreted glycoprotein that forms multimers and contains a leucine zipper and an olfactomedin domain. Mutations in myocilin are responsible for some forms of glaucoma, a neurodegenerative disease that is characterized by a continuous loss of optic nerve axons. Myocilin mRNA was detected by Northern blotting in RNA from the rat sciatic and ophthalmic nerves. By one- and two-dimensional gel electrophoresis of proteins from the rat and human sciatic nerves, myocilin was found to migrate at an isoelectric point (pI) of 5.2-5.3 and a molecular weight of 55-57 kDa. Immunohistochemistry showed immunoreactivity for myocilin in paranodal terminal loops of the nodes of Ranvier and outer mesaxons and basal/abaxonal regions of the myelin sheath. Double-labeling experiments with antibodies against myelin basic protein showed no overlapping, while overlapping immunoreactivity was observed with antibodies against myelin-associated glycoprotein. The expression of myocilin in the sciatic nerve became detectable at postnatal day (P) 15 and reached adult levels at P20. No or minor expression of myocilin mRNA was found in brain, spinal cord, and optic nerve. mRNA of myocilin was detected in schwannoma cells in situ, but at considerably lower levels than in myelinated nerves. Myocilin might significantly contribute to the structure of the myelin sheath in peripheral nerves.
Ohlmann
Andreas
A
Department of Anatomy, Molecular Anatomy and Embryology, University of Erlangen-Nürnberg, Erlangen, Germany.
Goldwich
Andreas
A
Flügel-Koch
Cassandra
C
Fuchs
Anne V
AV
Schwager
Konrad
K
Tamm
Ernst R
ER
D000375:Aging; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005123:Eye / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000235:genetics / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D000099179:Myocilin