Cell surface receptors and membrane proteins involved in exosome uptake

Cell surface receptors and membrane proteins involved in exosome uptake represent a diverse group of molecules that facilitate the internalization of extracellular vesicles (EVs) into recipient cells. This process is essential for horizontal gene transfer and protein signaling between cells (Mulcahy et al., 2014, PMID: 25317274). Key mediators include heparan sulfate proteoglycans (HSPGs), such as Syndecan-4, which serve as primary receptors for exosome docking (Christianson et al., 2013, PMID: 23940353). Additionally, tetraspanins (CD9, CD63, CD81) and integrins (e.g., αvβ3) are crucial for organizing membrane microdomains and determining the organ-specific targeting of exosomes (Hoshino et al., 2015, PMID: 26524530). Other proteins like T-cell immunoglobulin and mucin domain-containing protein 4 (TIM-4) recognize phosphatidylserine on the exosome surface to trigger phagocytosis (Miyanishi et al., 2007, PMID: 17914392). In disease states, these uptake mechanisms are often hijacked; for instance, cancer cells utilize specific integrins to prepare pre-metastatic niches, while neurodegenerative diseases like Alzheimer's use these pathways to spread tau or amyloid-beta aggregates. Therapeutic strategies involve using small molecules like heparin to block HSPG binding or inhibitors like amiloride to disrupt macropinocytosis-mediated uptake. Understanding these receptors is vital for both blocking pathological communication and engineering exosomes for targeted drug delivery.

Other names

Exosome uptake receptorsEV internalization proteinsExtracellular vesicle receptorsExosome docking proteins

Inhibition of ligand-receptor binding (e.g., heparin blocking HSPGs), disruption of endocytic machinery (e.g., dynamin inhibition by dynasore), and blockade of actin-dependent macropinocytosis (e.g., amiloride).