The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release

Claudia A. Escudero, Oscal M. Lazo, Carolina Galleguillos, Jose I. Parraguez, Maria A. Lopez-Verrilli, Carolina Cabeza, Luisa Leon, Uzma Saeed, Claudio Retamal, Alfonso Gonzalez, Maria Paz Marzolo, Bruce D. Carter, Felipe A. Court, Francisca C. Bronfman

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

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 postendocytic 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.

Original languageEnglish
Pages (from-to)1966-1979
Number of pages14
JournalJournal of Cell Science
Volume127
Issue number9
DOIs
Publication statusPublished - May 2014
Externally publishedYes

Keywords

  • Endocytosis
  • Mvbs
  • Neurotrophins
  • P75
  • Traffic

ASJC Scopus subject areas

  • Cell Biology

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