Phosphorylated olig1 localizes to the cytosol of oligodendrocytes and promotes membrane expansion and maturation.
Oligodendroglial cells undergo rapid transcriptional and dynamic morphological transformation in order to effectively myelinate neuronal axons. Olig1, a basic helix-loop-helix transcription factor, functions to promote the transcription of myelin-specific genes and promotes differentiation and (re)myelination. While the role for nuclear Olig1 is well established, the function for cytoplasmic Olig1 remains uncertain. We observe that translocation of Olig1 into the cytosol highly correlates with differentiation of oligodendrocytes both invivo and invitro. By enforcing expression of a nuclear-specific form of Olig1 into OPCs in a null-Olig1 background, we demonstrate that nuclear Olig1 is sufficient to facilitate MBP expression, but with greatly diminished membrane volume and area. We demonstrate that serine 138 in the helix-loop-helix domain of Olig1 is phosphorylated and that this form resides in the cytosol. Mutating serine 138 to alanine restricts Olig1 to the nucleus, facilitating MBP expression but limiting membrane expansion. However, a serine to aspartic acid mutation results in the cytoplasmic localization of Olig1 enhancing membrane expansion. Our results suggest a novel role for a phosphorylated cytosolic Olig1 in membrane expansion and maturation of oligodendrocytes.
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, China.
Jianqin
J
Niu
Feng
F
Mei
Lingyun
L
Wang
Shubao
S
Liu
Yanping
Y
Tian
Wei
W
Mo
Hongli
H
Li
Q Richard
QR
Lu
Lan
L
Xiao
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D051792:Basic Helix-Loop-Helix Proteins; C494786:Olig1 protein, mouse