Fig. 8.

Proposed model for TNF-α/PKC-mediated up-regulation of LEPRb protein level and cell surface expression. LEPRb in the biosynthetic pathway (blue) is sorted in the Golgi or trans-Golgi network (the blue oval labeled LEPRb), which directs LEPRb either to vesicles (the blue circle labeled LEPRb) destined to the plasma membrane (PM, light pink) or to a yet-to-be defined degradation compartment (purple hexagon). TNF-α/PKC activation increases the sorting of LEPRb toward the vesicles destined to the plasma membrane and decreases the sorting of LEPRb toward degradation compartment, resulting in concomitant increases in cellular protein level and cell surface expression of LEPRb. Endocytosis of LEPRb and trafficking of endocytic vesicles carrying LEPRb (the orange circle labeled LEPRb) to lysosomes (red and orange circles), which is regulated by endospanins (31), are not affected by TNF-α/PKC signaling.