Trends in Endocrinology & Metabolism
Intracellular trafficking of hormone receptors
Section snippets
Receptor endocytosis
In most cases, endocytosis of hormone receptors is accelerated by agonist binding, whereas nutrient receptors, such as LDL receptor (LDL-R) and transferrin receptor (TfR), are endocytosed constitutively at a rate independent of ligand occupancy 3, 4, 5. The best-identified pathway of receptor endocytosis is mediated by clathrin-coated vesicles (CCVs), first identified as the mechanism of LDL-R endocytosis 4, 5. TfR, EGF receptor (EGFR) and many GPCRs also internalize via CCVs 3, 4, 5. In yeast
Regulation of intracellular trafficking
Segregation of the receptor from its cognate ligand is important during endosomal sorting, as small recycling vesicles have a high surface to volume ratio, which favors the recycling of receptors, whereas dissociated ligands are retained in bulky endosomes [21]. Although this ‘geometric sorting mechanism’ can explain the targeting of dissociated ligands to lysosomes, differences in the recycling pathways and lysosomal targeting of plasma membrane receptors involves specific interactions with
Concluding remarks and future perspectives
Although the major intracellular trafficking pathways of plasma membrane receptors have been mapped, owing to the inherent complexity of the endosomal system, our understanding of these pathways and the signals that target molecules to different pathways is still incomplete. The diversity of intracellular trafficking routes also complicates the identification of the signals responsible for intracellular targeting of the receptors, and more studies are required to elucidate the exact mechanisms
Acknowledgements
This work was supported in part by a Collaborative Research Initiative Grant from the Wellcome Trust (069416/Z/02/Z), and by grants from the Hungarian Ministry of Public Health (ETT 036/2003) and the Hungarian Science Foundation (OTKA T-046445 and OTKA Ts-040865).
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