Bänfer Sebastian, Kutscher Sophie, Fleck Fenja, Dienst Martina, Preußer Christian, Pogge von Strandmann Elke, Jacob Ralf
Department of Cell Biology and Cell Pathology, Philipps University Marburg, Marburg, Germany.
Center for Tumor Biology and Immunology (ZTI), Institute for Tumor Immunology, Philipps University Marburg, Marburg, Germany.
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.
E-钙黏蛋白是一种参与上皮细胞间黏附与信号传导的跨膜蛋白，在从人体体液中分离出的外泌体组分中被发现。E-钙黏蛋白进入细胞外囊泡（EVs）的细胞机制尚未明确。在此，我们表明E-钙黏蛋白被整合到EVs的膜中，其细胞外结构域暴露于囊泡表面。这种招募依赖于运输所需的内体分选复合物I（ESCRT-I）组分Tsg101以及E-钙黏蛋白细胞质尾巴中一个高度保守的四肽P(S/T)AP晚期结构域基序，该基序介导与Tsg101的相互作用。该基序的突变导致相互作用丧失以及外泌体E-钙黏蛋白分泌显著减少。我们得出结论，晚期结构域介导的外泌体招募过程是由这种内源性非ESCRT跨膜蛋白发挥作用的。
