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. 2012 Jul 1;2(3):169-173.
doi: 10.4161/cl.21981.

Exosomes go with the Wnt

Kate Koles  1 , Vivian Budnik
Affiliations

Exosomes go with the Wnt

Kate Koles et al. Cell Logist. .

Abstract

Exosomes, small secreted microvesicles, are implicated in intercellular communication in diverse cell types, transporting protein, lipid and nucleic acid cargo that impact the physiology of recipient cells. Besides the signaling function of exosomes they also serve as a mechanism to dispose obsolete cellular material.1 Particularly exciting is the involvement of exosomal communication in the nervous system, as this has important implications for brain development and function. The properties of exosomes are also beginning to entice the biomedical community since they represent potentially novel avenues for the targeted delivery of customized exosome cargo, such as miRNAs, during disease. Our findings implicating exosomes in trans-synaptic communication emerged from the serendipitous observation that at the Drosophila larval neuromuscular junction (NMJ) the release of a signaling molecule, Wnt1/Wingless (Wg) and its binding partner Evenness Interrupted (Evi)/Wntless (Wls)/Sprint (Srt), were released by motorneurons in association with vesicles, which we postulated to be exosomes.2 In our most recent paper3 using in vivo analysis at the Drosophila NMJ as well as in cultured insect cells we formally demonstrate that Evi rides in exosomes that are released to the extracellular space and identify some of the players involved in their release. In addition, a proteomic analysis of exosomes highlights novel potential function of exosomes.

Keywords: Drosophila; Evi/Wntless/GPR177/mig-14; RNA-binding proteins; Rab11; Syntaxin 1A; Wingless; Wnt; exosomal proteome; exosome release; local translation; neuromuscular junction; retromer.

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Figures

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Figure 1. Wg rides on exosomes. Schematic representation of Evi-exosome mediated Wg release at Drosophila larval NMJs. Wg carried by Evi-exosomes is sorted into multivesicular bodies at synaptic terminals. Multivesicular bodies fuse with the presynaptic membrane releasing their exosomal content to the cisternae of underlying subsynaptic reticulum, where DFrizzled2 receptors are found. This fusion occurs at sites that are likely distinct from active zones, the periactive zones. In contrast to synaptic vesicles, which use Rab3 and Syntaxin1A for targeting and release of the vesicles at the active zones, the release of exosomes requires Rab11, its effector Myosin5 and the target-SNARE Syntaxin1A. Synaptobrevin is a vesicular-SNARE that functions in synaptic vesicle release and fusion via its interaction with Syntaxin1A, however the v-SNARE on multivesicular bodies has not yet been identified. Potential fates of the released Evi-exosomes are also depicted, however for a more detailed discussion on the role of postsynaptic Evi, see reference .
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Figure 2. The short and long of Evi. ClustalW2 alignment of the region near the last intracellular loop of Evi/Wls/GPR177/mig-14, from the species indicated on the left, showing that the alternative splicing of an extra exon in Drosophila melanogaster Evi-long isoform (D.mel long) leads to the disruption of the conserved YXXΦ endocytosis domain. All known vertebrate and mammalian species only produce the protein corresponding to the Drosophila melanogaster Evi-short isoform (D.mel shor). Black shading indicates identical amino acids, gray shading denotes conserved physic-chemical properties, while white background corresponds to lack of conservation. Although in this drawing Evi is depicted as a seven pass transmembrane protein, the exact number of membrane spanning domains (7 or 8) is yet to be determined.
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