title: Endosomes: a legitimate platform for the signaling train.
abstract: Although long regarded as a conduit for the degradation or recycling of cell surface receptors, the endosomal system is also an essential site of signal transduction. Activated receptors accumulate in endosomes, and certain signaling components are exclusively localized to endosomes. Receptors can continue to transmit signals from endosomes that are different from those that arise from the plasma membrane, resulting in distinct physiological responses. Endosomal signaling is widespread in metazoans and plants, where it transmits signals for diverse receptor families that regulate essential processes including growth, differentiation and survival. Receptor signaling at endosomal membranes is tightly regulated by mechanisms that control agonist availability, receptor coupling to signaling machinery, and the subcellular localization of signaling components. Drugs that target mechanisms that initiate and terminate receptor signaling at the plasma membrane are widespread and effective treatments for disease. Selective disruption of receptor signaling in endosomes, which can be accomplished by targeting endosomal-specific signaling pathways or by selective delivery of drugs to the endosomal network, may provide novel therapies for disease.
authors.affiliation: Department of Surgery, University of California, San Francisco, CA 94143, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Murphy
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Padilla
authors.forename: Burcu
authors.initials: B
authors.lastname: Hasdemir
authors.forename: Graeme S
authors.initials: GS
authors.lastname: Cottrell
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Bunnett
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology; D054875:Ubiquitination / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D051193:Toll-Like Receptors; D020794:Receptor Protein-Tyrosine Kinases; D010447:Peptide Hydrolases