Signaling via immunoglobulin Fc receptors induces oligodendrocyte precursor cell differentiation.
Dramatic changes in morphology and myelin protein expression take place during the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the differentiation process. Molecules that could induce Fyn signaling have not been studied. Such molecules are promising therapeutic targets in demyelinating diseases. We provide evidence that the common gamma chain of immunoglobulin Fc receptors (FcRgamma) is expressed in OPCs and has a role in triggering Fyn signaling. FcRgamma cross-linking by immunoglobulin G on OPCs promotes the activation of Fyn signaling and induces rapid morphological differentiation with upregulation of myelin basic protein (MBP) expression levels. Mice deficient in FcRgamma are hypomyelinated, and a significant reduction in MBP content is evident. Our findings indicate that the FcRgamma-Fyn-MBP cascade is pivotal during the differentiation of OPCs into myelinating oligodendrocytes, revealing an unexpected involvement of immunological molecules.
Nakahara
Jin
J
Glial Cell Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi, 173-0015, Tokyo, Japan. nakaharajin@anet.ne.jp
Tan-Takeuchi
Kyoko
K
Seiwa
Chika
C
Gotoh
Mari
M
Kaifu
Tomonori
T
Ujike
Azusa
A
Inui
Masanori
M
Yagi
Takeshi
T
Ogawa
Masaharu
M
Aiso
Sadakazu
S
Takai
Toshiyuki
T
Asou
Hiroaki
H
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004789:Enzyme Activation; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D017479:Receptors, Platelet-Derived Growth Factor; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn