The Functional Importance of Tetraspanins in Exosomes

Abstract

Exosomes are small vesicles that derive from the release of limiting membranes from multivesicular bodies (MVB). They carry and transfer selected membrane and cytoplasmic proteins, mRNA, and microRNA into target cells. Due to this shipping of information, exosomes are considered to be a most promising therapeutic tool for multiple diseases.Whereas knowledge on the composition of exosomes is rapidly increasing, the mode of selective recruitment into exosomes as well as target cell selection is poorly understood. We suggest that at least part of this task is taken over by tetraspanins. Tetraspanins are a highly conserved family of proteins that are involved in a multitude of biological processes. This is a sequel of their special arrangement in glycolipid-enriched membrane microdomains, where tetraspanins form a net between themselves and neighboring molecules. These membrane domains, called tetraspanin-enriched microdomains (TEM), are prone for internalization. The early endosomes become integrated into MVBs, the primary source of exosomes. Thereby tetraspanin and tetraspanin-associated molecules become enriched in exosomes.We will discuss here how the protein assembly of exosomes and possibly the recruitment of microRNA can be regulated by tetraspanins and how tetraspanins account for target cell selection and uptake of exosomes.Exosomes herald an unanticipated powerful path of cell-cell communication. An answer to how exosomes collect and transfer information will allow the use of nature's concept to cope with malfunctions. Abbreviations ADAMA disintegrin and metalloproteinase AP Adapter protein APC

Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles

“…After ultracentrifugation, the nanovesicles isolated from these OSCC cells were then characterized and showed typical morphology and markers of small EVs. The protein markers such as transmembrane tetraspanins CD9, CD63, CD81 and heat shock proteins HSC70 were used in this study to perform identity verification of the isolated vesicles and they were found to share the same characteristics as small EVs including exosomes derived from many cell types [19,20].…”

To Protect and to Preserve: Novel Preservation Strategies for Extracellular Vesicles

“…Although, there is still debate as to whether MBVs possess all of the characteristics required to be defined as an EV, there is also evidence that EVs can bind to ECM components; for example, a study by Narayanan et al showed binding of MSC-derived EVs to bind to both fibronectin and collagen type I in the ECM ( Narayanan et al, 2016 ). Such interactions between EVs and the ECM are likely mediated by adhesion receptors, known to be present on the exosomal membrane, including integrins, tetraspanins, and ICAM-1 ( Escola et al, 1998 ; Thery et al, 1999 , 2001 ; Rana and Zoller, 2013 ).…”

Endogenous Alpha-Synuclein is Essential for the Transfer of Pathology by Exosome-Enriched Extracellular Vesicles, Following Inoculation with Preformed Fibrils in vivo

“…More specifically, the analyzed exosomal fractions were enriched in adhesion molecules such as tetraspanins (eg. CD47, CD81, CD82, and CD9) and integrins, membrane transport and fusion proteins, including annexins, flotillins, and Rabs, ESCRT, heat shock and signaling proteins, cytoskeleton and ion transport components, as well as metabolic enzymes ( Supplementary Table 2 ); all these proteins have been found, by MS/MS analysis, to comprise characteristic components of exosomes from different cell types [ 47 ], [ 48 ]. Consistently, screening of the 614 identified exosome-specific proteins with the Vesiclepedia and ExoCarta databases showed a 71 % and 76% overlap, respectively ( Supplementary Fig.…”

“…Importantly, proteomic analysis revealed that almost half of the identified cargo proteins were classified in the extracellular exosome GO, demonstrating a substantial overlap with known extracellular vesicle databases (Vesiclepedia, and ExoCarta), and that brain tissue was identified as the main source of their origin. Taken all together, we established that the isolated vesicular preparations meet the criteria of intact brain extracellular vesicles enriched in exosomes [ 8 , 47 , 48 ] and thus ensured that any ExE-EV-related phenotype could not be attributed to the heterogeneous starting material. Importantly, PFF injection did not alter the quantity, shape and size distribution of the isolated ExE-EVs in both WT and α-Syn KO background, in comparison to the respective controls.…”