Abstract
Extracellular membrane vesicles (EMVs) are nanometer sized vesicles, including exosomes and microvesicles capable of transferring DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, and lipids among cells without direct cell-to-cell contact, thereby representing a novel form of intercellular communication. Many cells in the nervous system have been shown to release EMVs, implicating their active roles in development, function, and pathologies of this system. While substantial progress has been made in understanding the biogenesis, biophysical properties, and involvement of EMVs in diseases, relatively less information is known about their biological function in the normal nervous system. In addition, since EMVs are endogenous vehicles with low immunogenicity, they have also been actively investigated for the delivery of therapeutic genes/molecules in treatment of cancer and neurological diseases. The present review summarizes current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervous system in the foreseeable future.
Highlights
Ligand-receptor interaction and direct cell–cell contacts via specialized physical conduits, such as gap junctions and membrane nanotubes, have long been considered as the predominant means of intercellular communication (Davis and Sowinski, 2008; Goodenough and Paul, 2009)
Additional investigations are needed to determine if distinct MVB or ILV populations destined for degradation or exocytic release are present, as well as whether a common exosomal trafficking mechanism exists in all cell types (Mathivanan et al, 2010)
While an impressive number of exciting findings have been made in the past few years, many questions still remain to be answered with respect to different aspects of Extracellular membrane vesicles (EMVs) biology
Summary
Ligand-receptor interaction and direct cell–cell contacts via specialized physical conduits, such as gap junctions and membrane nanotubes, have long been considered as the predominant means of intercellular communication (Davis and Sowinski, 2008; Goodenough and Paul, 2009). Unlike other types of EMVs that are directly shed/released from the plasma membrane, exosomes are formed by a series of processes beginning with inward invagination of clathrin-coated microdomains on the plasma membrane (Denzer et al, 2000) Once these vacuoles have entered the cell, the Endosomal Sorting Complex Required for Transport (ESCRT) facilitates the development of the invaginated vacuoles carrying ubiquitinated cargos into early endosomes. This is followed by a secondary invagination of vesicles (termed intraluminal vesicles, ILVs), into the endosomes where they accumulate with subsequent maturation of the complex into large multivesicular bodies (MVBs; Denzer et al, 2000). In contrast to the endocytotic origin of www.frontiersin.org
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