Extracellular Vesicles Signals: Exosomes
How cells manufacture proteins for export, how cells manufacture vesicles that are exported outside the cells, how human cells secrete small RNAs in extracellular vesicles and how these vesicles capture small RNA molecules is a huge exciting area of scientific investigation.
Looking specifically at the EVs that we call exosomes, there is now evidence that the exosomes may mediate the transfer of information between cells, for example in the human body, that may influence development or may be subverted in diseased states, for instance, in the progression of cancer or metastatic cancer. What do they look like, what do they contain, how are they manufactured inside of nucleated human cells? These are all current questions being answered and further studied.
Extracellular vesicles are carriers of unconventional signals. If we were to look at a diagram the cells would look like many other vesicles, with a bilayer of around 90nm in diameter.
It would have some membrane proteins, some of which integral, that span the membrane several times. There are small proteins and other small molecules in the luminal interior of the vesicle but what distinguishes these vesicles from those that are found inside of cells, and that are responsible for secretion, is the presence of small RNAs. Micro RNAs that are believed to be involved in the control of gene expression, or even transfer RNAs, or other unusual RNAs are housed sometimes in high chemical concentration in the interior of these vesicles. These vesicles can be expelled outside of cells where the vesicle may be targeted to distal tissue and taken up by fusion at the cell surface or by internalisation of endocytosis.
One idea about how these organisms are made; inside of nucleated cells through a pathway used when cells internalize receptors and deliver them, eventually for destruction, by proteolysis in an organelle is called the lysosome. The process often begins when the cells surface receptor is taken up into a membrane called an endosome.
Often these cell surface receptors have a chemical tag, a small peptide called ubiquitin. This tag protein marks a membrane protein for destruction. It is captured into membrane that pinches into the interior of the endosome and invagination into the interior of the endosome results in a small intraluminal vesicle. This process can continue for some time to build up an endosomal structure that has many vesicles and this structure is called the multivesicular body. In more recent years it has become known that this multivesicular body targets and delivers these interluminal vesicles to the lysosome where the content of these vesicles may be degraded into amino acids and sugars, pumped back into the cytoplasm of the cell, to be reused in biosynthetic processes. It has been only in the last 15 to 20 years that sometimes and by means that are not fully clear these multivesicular bodies may actually travel in the cell surface and fuse where the intraluminal vesicles, now, are expelled to the outside of the cell as a bolus of vesicles, often call EVs or exosomes. As such, these vesicles may then be targeted to distant tissues in the body and the molecules that are contained within them may then be a target cell to change gene expresssion or change signalling by that cell. Alternatively, this export of vesicles may be another way that the cell has simply of disposing of these vesicles, not for some positive function but just to get rid of them. These two alternatives still remain viable.