Research progress on the interaction mechanisms and functions between exosomes and the cytoskeleton.

Exosomes, as key mediators of intercellular communication, play a central regulatory role in cellular physiological and pathological processes through their dynamic interaction with the cytoskeleton. The cytoskeleton is a dynamic network composed of microtubules, microfilaments, and intermediate filaments. Microtubules provide track support for the directional transport of MVBs. Microfilament rearrangement generates contractile forces that promote MVB fusion with the plasma membrane. Therefore, the cytoskeleton directly participates in the biogenesis, intracellular transport, and secretion of exosomes. Moreover, cytoskeletal dynamics, coordinated by molecules such as Rab GTPases, affect exosome secretion efficiency. Conversely, exosomes carry bioactive molecules such as proteins, nucleic acids, and lipids. These molecules can regulate cytoskeletal rearrangement in recipient cells by modulating signaling pathways like the TGF-β/Smad signaling pathway and the RhoA/ROCK signaling pathway. Consequently, they influence target cell functions like morphology maintenance, migration, and proliferation. Dysregulation of this interaction is closely related to the progression of various diseases, including tumors and neurodegenerative diseases. For instance, disrupting the dynamic structure of the cytoskeleton or blocking the cytoskeletal remodeling process can significantly reduce exosome secretion, while abnormal exosome transfer disrupts cytoskeletal homeostasis. Current research still faces challenges, such as unresolved details of the molecular regulatory network and a lack of in-depth mechanistic validation in in vivo models. Future studies need to explore in depth novel regulatory factors and signaling pathways and investigate disease diagnosis and treatment strategies based on this interaction. This will provide a theoretical basis and innovative ideas for the prevention and treatment of related diseases.