Exosomes, Ectosomes and the Two Together. Physiology and Pathology

摘要

Eukaryotic cells release to the extracellular space two types of vesicles which have attracted great interest, early on for their complex generation and function, and more recently for their role in multiple diseases including cancer. Previous studies have revealed ample information about these vesicles, especially the exosomes. In this review, I report the developments that have occurred during the last few years. Small vesicles first accumulated within large endocytic cisternae and are then converted into multivesicular bodies. Upon exocytosis of the latter, the released vesicles are defined as exosomes. Ectosomes, which are known only in scant detail, are larger vesicles that pinch off rapidly from the plasma membrane. The rate of this release increases markedly upon appropriate cell stimulation. Both types of vesicle are delimited by a membrane that delimits a condensed cargo composed by proteins, mRNAs, miRNAs, and DNA, which are sorted from the cytoplasm. Several proteins, previously presented as markers of either vesicle, are common to both. Today, only a few markers are accepted. Upon their release, both exosomes and ectosomes are addressed to specific target cells, where they bind and surface roll for several seconds. Later, vesicles undergo outside/in fusion to the plasma membrane by a process analogous to the fusions of retroviruses. Fusion results in the horizontal transfer of cargoes that govern changes of the genome and of protein expression, up to the reprogramming of cell structure and function. In many physiological functions, the two types of vesicles operate together. Their mixtures play specific roles in processes such as blood coagulation, angiogenesis, innate and acquired immunity, synaptic transmission. Currently, some pathology investigations are focused on the diagnosis of diseases through recognition of specific vesicles and on preliminary therapy with targeted vesicles loaded with molecules aggressive to diseased cells.