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Consequently, in case of receptors containing GLP-1 Y250/252A mutations, which prevent the localization of GLP-1R on the plasmamembrane and the binding of GLP-1, the intracellular signaling is lost ( The fate of a receptor after activation is another important mechanism to control its signaling capacity: GLP-1R undergoes agonist-mediated endocytosis, which may lead either to recycle the receptor back to the plasma membrane or to degradative pathway ( GLP-1R internalization is also important for the spatiotemporal control of signaling