The localization and non-genomic function of the membrane-associated estrogen receptor in oligodendrocytes.
There is general acceptance that the estrogen receptor can act as a transcription factor. However, estrogens can also bind to receptors that are located at the plasma membrane and stimulate rapid intracellular signaling processes. We recently showed that a membrane-associated estrogen receptor (mER) is present within myelin and at the oligodendrocyte (OL) plasma membrane. To understand the physiological function of mER in OLs, we investigated its cellular localization and involvement in rapid signaling in CG4 cells and OL primary cultures. An ERalpha was expressed along the lacy network of veins in the membrane sheets and in the perikaryon and nucleus in OLs. ERbeta was located in the nucleus, and to a lesser extent along the veins. The expression of ERalpha and ERbeta in OL membranes was confirmed by Western analysis of isolated membranes. OL membranes mainly had truncated forms of ERalpha, 53 and 50 kDa, in addition to some 65 kDa form, whereas ERbeta was a 54 kDa form. CG4 cells and OLs were pulsed with 17alpha- and 17beta-estradiol for various times and the total lysates were analyzed for phosphorylated kinases. Both 17alpha- and 17beta-estradiol elicited rapid phosphorylation of p42/44MAPK, Akt, and GSK-3beta within 8 min. This rapid signaling is consistent with estradiol ligation of a membrane form of ER. Since 17alpha-estradiol is produced at higher concentrations than 17beta-estradiol in the brain of both sexes, signaling via 17alpha-estradiol-liganded mER may have an important function in OLs.
Hirahara
Yukie
Y
Division of Molecular Structure and Function, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Matsuda
Ken-Ichi
K
Gao
Wen
W
Arvanitis
Dina N
DN
Kawata
Mitsuhiro
M
Boggs
Joan M
JM
D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000032:analysis / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000032:analysis / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D004958:Estradiol