Late domain dependent E-cadherin recruitment into extracellular vesicles

Front Cell Dev Biol. 2022 Sep 7;10:878620. doi: 10.3389/fcell.2022.878620. eCollection 2022.


E-cadherin, a transmembrane protein involved in epithelial cell-cell adhesion and signaling, is found in exosomal fractions isolated from human body fluids. A cellular mechanism for recruitment of E-cadherin into extracellular vesicles (EVs) has not yet been defined. Here, we show that E-cadherin is incorporated into the membrane of EVs with the extracellular domain exposed at the vesicle surface. This recruitment depends on the endosomal sorting complex required for transport I (ESCRT-I) component Tsg101 and a highly conserved tetrapeptide P(S/T)AP late domain motif in the cytoplasmic tail of E-cadherin that mediates interaction with Tsg101. Mutation of this motif results in a loss of interaction and a dramatic decrease in exosomal E-cadherin secretion. We conclude, that the process of late domain mediated exosomal recruitment is exerted by this endogenous non-ESCRT transmembrane protein.

Keywords: E-cadherin; ESCRT (endosomal sorting complex required for transport); exosomes; extracellular vesicles; late domain; multivesicular bodies (MVB).