Exosomal transfer of proteins and RNAs at synapses in the nervous system

Background: Many cell types have been reported to secrete small vesicles called exosomes, that are derived from multivesicular bodies and that can also form from endocytic-like lipid raft domains of the plasma membrane. Secretory exosomes contain a characteristic composition of proteins, and a recent report indicates that mast cell exosomes harbor a variety of mRNAs and microRNAs as well. Exosomes express cell recognition molecules on their surface that facilitate their selective targeting and uptake into recipient cells. Results: In this review, I suggest that exosomal secretion of proteins and RNAs may be a fundamental mode of communication within the nervous system, supplementing the known mechanisms of anterograde and retrograde signaling across synapses. In one specific scenario, exosomes are proposed to bud from the lipid raft region of the postsynaptic membrane adjacent to the postsynaptic density, in a manner that is stimulated by stimuli that elicit long-term potentiation. The exosomes would then transfer newly synthesized synaptic proteins ( such as CAM kinase II alpha) and synaptic RNAs to the presynaptic terminal, where they would contribute to synaptic plasticity. Conclusion: The model is consistent with the known cellular and molecular features of synaptic neurobiology and makes a number of predictions that can be tested in vitro and in vivo. Open peer review: Reviewed by Etienne Joly, Gaspar Jekely, Juergen Brosius and Eugene Koonin. For the full reviews, please go to the Reviewers' comments section.