Uptake and recycling of pro-BDNF for transmitter-induced secretion by cortical astrocytes

Matteo Bergami, Spartaco Santi, Elena Formaggio, Cinzia Cagnoli, Claudia Verderio, Robert Blum, Benedikt Berninger, Michela Matteoli, Marco Canossa

Research output: Contribution to journalArticlepeer-review

Abstract

Activity-dependent secretion of brain-derived neurotrophic factor (BDNF) is thought to enhance synaptic plasticity, but the mechanisms controlling extracellular availability and clearance of secreted BDNF are poorly understood. We show that BDNF is secreted in its precursor form (pro-BDNF) and is then cleared from the extracellular space through rapid uptake by nearby astrocytes after θ-burst stimulation in layer II/III of cortical slices, a paradigm resulting in long-term potentiation of synaptic transmission. Internalization of pro-BDNF occurs via the formation of a complex with the pan-neurotrophin receptor p75 and subsequent clathrin-dependent endocytosis. Fluorescence-tagged pro-BDNF and real-time total internal reflection fluorescence microscopy in cultured astrocytes is used to monitor single endocytic vesicles in response to the neurotransmitter glutamate. We find that endocytosed pro-BDNF is routed into a fast recycling pathway for subsequent soluble NSF attachment protein receptor-dependent secretion. Thus, astrocytes contain an endocytic compartment competent for pro-BDNF recycling, suggesting a specialized form of bidirectional communication between neurons and glia.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalJournal of Cell Biology
Volume183
Issue number2
DOIs
Publication statusPublished - Oct 20 2008

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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