title: The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release.
abstract: The p75 neurotrophin receptor (p75, also known as NGFR) is a multifaceted signalling receptor that regulates neuronal physiology, including neurite outgrowth, and survival and death decisions. A key cellular aspect regulating neurotrophin signalling is the intracellular trafficking of their receptors; however, the post-endocytic trafficking of p75 is poorly defined. We used sympathetic neurons and rat PC12 cells to study the mechanism of internalisation and post-endocytic trafficking of p75. We found that p75 internalisation depended on the clathrin adaptor protein AP2 and on dynamin. More surprisingly, p75 evaded the lysosomal route at the level of the early endosome, instead accumulating in two different types of endosomes, Rab11-positive endosomes and multivesicular bodies (MVBs) positive for CD63, a marker of the exosomal pathway. Consistently, depolarisation by KCl induced the liberation of previously endocytosed full-length p75 into the extracellular medium in exosomes. Thus, p75 defines a subpopulation of MVBs that does not mature to lysosomes and is available for exosomal release by neuronal cells.
authors.affiliation: Faculty of Biological Sciences, Physiology Department, Pontificia Universidad Católica, Santiago, CP 8331010, Chile.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Escudero
authors.forename: Oscal M
authors.initials: OM
authors.lastname: Lazo
authors.forename: Carolina
authors.initials: C
authors.lastname: Galleguillos
authors.forename: Jose I
authors.initials: JI
authors.lastname: Parraguez
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lopez-Verrilli
authors.forename: Carolina
authors.initials: C
authors.lastname: Cabeza
authors.forename: Luisa
authors.initials: L
authors.lastname: Leon
authors.forename: Uzma
authors.initials: U
authors.lastname: Saeed
authors.forename: Claudio
authors.initials: C
authors.lastname: Retamal
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Marzolo
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Carter
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Court
authors.forename: Francisca C
authors.initials: FC
authors.lastname: Bronfman
mesh_terms: D000818:Animals; D011992:Endosomes / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D057146:Multivesicular Bodies / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D034622:RNA Interference; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat
keywords: Endocytosis; MVBs; Neurotrophins; Traffic; p75