Schematic diagram illustrating estradiol-mediated ERα trafficking at the membrane. ERα-mGluR1a (blue-orange) complexes are inserted into the membrane of an exocytotic vesicle. These are associated through interactions with calveolin. Estradiol (red spheres) induces vesicle docking with the membrane and insertion of the ERα-mGluR1a complex into the membrane. Exposed to the extracellular space, estradiol binds to ERα, transactivating mGluR1a and initiating cell signaling. Estradiol-activated ERα-mGluR1a complexes are then internalized via a clathrin-mediated process and fuse with early endosomes where the estradiol is released from ERα. The ERα-mGluR1a complex can then be recycled to the membrane or degraded. Initially, there appears to be a recycling of the ERα-mGluR1a complex, but with continued stimulation, the process shifts toward degradation.
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