Proteomic analysis of microglia-derived exosomes: Metabolic role of the aminopeptidase CD13 in neuropeptide catabolism

Vesicle transport is a fundamental mechanism of communication in the CNS. In this study we characterized a novel type of vesicle released by murine brain microglial cells: microglial exosomes. Analysis of their protein content identified several enzymes, chaperones, tetraspanins, and membrane receptors previously reported in B cells and dendritic cell-derived exosomes. Additionally, microglia-derived exosomes expressed the aminopeptidase CD13 and the lactate transporter MCT-1. Exosomal CD13 was metabolically active in cleaving leucine- and methionine-enkephalins peptides by releasing the N-terminal tyrosine. Cleaved neuropeptides were unable to bind to the neuronal opioid receptor as assessed by cAMP response. Microglial exosomal vesicles may represent an important, previously unrecognized, cellular communication system in an organ in which cell motility is highly restricted.