Fig. 9 | Scientific Reports

Fig. 9

From: The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling

Fig. 9

Proposed mechanism of MARCH1-induced downregulation of GABAB receptors under ischemic conditions. Under normal physiological conditions, GABAB receptors are constitutively endocytosed and most internalized receptors are recycled to the plasma membrane, whereas a fraction is degraded in lysosomes. Under ischemic conditions, upregulated MARCH1 interacts with GABAB receptors and ubiquitinate them. This inhibits recycling of endocytosed GABAB receptors. Blocking recycling causes rapid removal of GABAB receptors from the plasma membrane and triggers their lysosomal degradation. Application of M1-Pep after ischemic stress inhibits the interaction of MARCH1 with GABAB receptors. This re-establishes recycling of the receptors to the plasma membrane and normalizes enhanced lysosomal degradation of GABAB receptors, resulting in normal plasma membrane expression of GABAB receptors and inhibition progressive neuronal death. The figure was created using https://www.biorender.com/.

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