Resolving sorting mechanisms into exosomes

Abstract

The complexity of mechanisms driving protein sorting into exosomes is only beginning to emerge. In a paper recently published in Cell Research, Roucourt et al. report that trimming of heparan sulfate side chains of syndecans by endosomal heparanase facilitates sorting into exosomes by the formation of tight syndecan clusters that are recruited by the multivalent adaptor syntenin to the ALIX-ESCRT sorting machinery at endosomes.

Figure 1

Syndecans are processed at endosomes, first by trimming associated heparin sulfate site chains, followed by proteolytic cleavage. Clustered syndecan can now be recruited by multivalent syntenin, which on its turn is coupled to the ESCRT machinery via ALIX. Similarly, CD63 is recruited by syntenin, and with it presumably other membrane proteins that are associated with tetraspanin webs. Heparanase also stimulates sorting of CD63, indicating that the two pathways driven by syndecan and CD63 are somehow integrated.