VDAC and ERalpha interaction in caveolae from human cortex is altered in Alzheimer's disease.
Voltage-dependent anion channel (VDAC) is a mitochondrial porin also found in the neuronal membrane (pl-VDAC), where its function may be related to redox homeostasis and apoptosis. Murine models have evidenced pl-VDAC into caveolae in a complex with estrogen receptor alpha (mERalpha), which participates in neuroprotection against amyloid beta (Abeta), and whose integration into this hydrophobic domain remains unclear. Here, we have demonstrated in caveolae of human cortex and hippocampus the presence of pl-VDAC and mERalpha, in a complex with scaffolding caveolin-1 which likely provides mERalpha stability at the plasma membrane. In Alzheimer's disease (AD) brains, VDAC was accumulated in caveolae, and it was observed in dystrophic neurites of senile plaques, whereas ERalpha was expressed in astrocytes surrounding the plaques. Together with previous data in murine neurons demonstrating the participation of pl-VDAC in Abeta-induced neurotoxicity, these data suggest that the channel may be involved in membrane dysfunctioning observed in AD neuropathology.
Ramírez
Cristina M
CM
Laboratory of Cellular Neurobiology, Department of Physiology, Faculty of Medicine and Institute of Biomedical Technologies, University of La Laguna, 38071 Sta. Cruz de Tenerife, Spain.
González
Miriam
M
Díaz
Mario
M
Alonso
Rafael
R
Ferrer
Isidre
I
Santpere
Gabriel
G
Puig
Berta
B
Meyer
Gundela
G
Marin
Raquel
R
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
D051242:Caveolin 1; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D050994:Voltage-Dependent Anion Channels