Seminar

Myelin membrane traffic and the role of exosome secretion in axon-glia interaction.

Eva Maria Krämer- Albers, PhD

Brain function depends on coordinated interactions between neurons and glial cells. Oligodendrocytes ensheath axons with the myelin membrane and furthermore maintain long-term axonal integrity by an unknown pathway. We are studying myelin membrane traffic and its control by axon-glia interaction. Endocytic sorting and recycling appears to be a common mode of myelin protein trafficking. The major myelin membrane protein PLP is recycling through late endosomal compartments and multivesicular bodies (MVB). MVB fusion with the oligodendroglial plasma membrane results in secretion of exosomes into the extracellular space. These exosomes carry myelin proteins in addition to genuine exosome proteins and distinct species of RNA. Intriguingly, oligodendrocyte exosome release is stimulated by electrically active neurons via neurotransmitter secretion and activation of glial neurotransmitter receptors. Moreover, neurons internalize oligodendrocyte-derived exosomes by endocytosis and recipient neurons functionally recover the exosome cargo. Functional studies indicate that the transfer of oligodendrocyte-derived exosomes protects neurons from stress and starvation. We propose that oligodendroglial exosomes participate in bidirectional neuron-glia communication and mediate the transfer of bioactive molecules from glia to neurons. The signal-mediated transfer of exosomes from glia to neurons may be implicated in neuroprotection and glial maintenance of axonal integrity.