Estradiol facilitates neurite maintenance by a Src/Ras/ERK signalling pathway.
Different reports suggest the estrogens are involved in neuritic outgrowth, maintenance of dendritic morphology and spine formation in the CNS. However, the molecular mechanisms regulated by estrogens on neuronal integrity are not fully understood. We have addressed the relationship between 17beta-estradiol-dependent ERK pathway stimulation and the maintenance of neuritic morphology in cerebellar granule cell cultures (CGC). We report that 17beta-estradiol clearly activates ERK phosphorylation in CGC cultured in low potassium via ERalpha localized in the plasma membrane and without the activation of the insulin-like growth factor-I receptor. 17beta-estradiol activates the ERK pathway through Ras-dependent Src kinase activity. A concomitant activation of the cAMP-response element-binding protein (CREB) is observed. Moreover, we demonstrate that 17beta-estradiol-mediated ERK activation is involved in the maintenance of neuritic arborisation and neuronal morphology in proapoptotic conditions.
Miñano
Alfredo
A
Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Spain.
Xifró
Xavier
X
Pérez
Virgili
V
Barneda-Zahonero
Bruna
B
Saura
Carlos A
CA
Rodríguez-Alvarez
José
J
D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D004958:Estradiol; D050882:CREB-Binding Protein; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins