title: N-cadherin is a novel ERα anchor that protects against 6-OHDA damage to dopaminergic cells.
abstract: Parkinson's disease is a neurodegenerative disorder caused by the selective loss of dopaminergic (DA) neurons. In this study, we investigated the protective roles of glial cell line-derived neurotrophic factor (GDNF) and 17β-estradiol (E2) in the neuron cell line MN9D following treatment with 6-hydroxydopamine. This result showed that phosphorylation of protein kinase B (Akt) was significantly increased in treated MN9D cells following co-application of GDNF and E2 compared with only GDNF or E2. Moreover, GDNF enhanced the E2-induced translocation of estrogen receptor α (ERα) from the cytosol to the membrane. Immunoprecipitation experiments showed that the translocated ERα interacted with neural cadherin (N-cadherin) in the membrane. Site-directed mutagenesis of Tyr860 (Y860) in N-cadherin inhibited its interaction with ERα. Combined with the fact that GDNF can stimulate N-cadherin Y860 phosphorylation, we hypothesize that N-cadherin is a novel anchor for ERα, and phosphorylation at Y860 further increases ER's capacity to activate the neuroprotective phosphatidyl inositol-3 kinase/Akt pathway. This study provides evidence that co-application of GDNF and E2 exert important protective effects on DA neurons by increasing the interaction between ERα and N-cadherin.
authors.affiliation: Department of Neurobiology & Anatomy, Xuzhou Medical College, Xuzhou Tongshanlu No. 209, Xuzhou, Jiangsu, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Zixiao
authors.initials: Z
authors.lastname: Shi
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Dianshuai
authors.initials: D
authors.lastname: Gao
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D051379:Mice; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D015820:Cadherins; D047628:Estrogen Receptor alpha; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D019000:Phosphotyrosine; D004958:Estradiol; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt