Signaling Pathways in Exosomes Biogenesis, Secretion and Fate

Abstract

Exosomes are small extracellular vesicles (30–100 nm) derived from the endosomal system, which have raised considerable interest in the last decade. Several studies have shown that they mediate cell-to-cell communication in a variety of biological processes. Thus, in addition to cell-to-cell direct interaction or secretion of active molecules, they are now considered another class of signal mediators. Exosomes can be secreted by several cell types and retrieved in many body fluids, such as blood, urine, saliva and cerebrospinal fluid. In addition to proteins and lipids, they also contain nucleic acids, namely mRNA and miRNA. These features have prompted extensive research to exploit them as a source of biomarkers for several pathologies, such as cancer and neurodegenerative disorders. In this context, exosomes also appear attractive as gene delivery vehicles. Furthermore, exosome immunomodulatory and regenerative properties are also encouraging their application for further therapeutic purposes. Nevertheless, several issues remain to be addressed: exosome biogenesis and secretion mechanisms have not been clearly understood, and physiological functions, as well as pathological roles, are far from being satisfactorily elucidated.

STIM1/ORAI1-mediated Ca2+ Influx Regulates Enolase-1 Exteriorization

“…Exosomes derived from the tumor may transfer oncogenes and proangiogenic signals to stromal cells and thus promote tumor vascularization. Additionally, they can contribute to stromal remodeling and tumor cell invasion by carrying active matrix metalloproteinases (50). In view of these results, it is tempting to speculate that exosomal ENO-1 could contribute to tumor progression either by concentrating proteolytic activity on the cancer cell surface or by enlarging the cytoplasmic pool of ENO-1 and, by doing this, regulating expression of the genes involved in cell growth, migration, and inflammation.…”

“…Exosomes may influence the behavior of target cells in multiple ways. For example, they can activate signaling complexes by direct stimulation of target cells or deliver genetic information/proteins to recipient cells (50). Thus, exosomes were found to regulate a variety of processes, including cell proliferation, differentiation, migration, and invasion (50).…”

“…A growing body of evidence suggests that exosomes may act as regulators of cell to cell communication. This concept is based on the finding that exosomes released from a given cell type may interact with other cells, leading to target cell stimulation (50). Exosomes may influence the behavior of target cells in multiple ways.…”

Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

“…4,5 Although fusion of exosome-containing multivesicular bodies with lysosomes has been considered a mechanism for elimination of unnecessary exosomal proteins, autolysosomal dysfunction of neurons in AD may result in addition of lysosomal proteins to exosomal cargo for facilitation of their removal from neurons. 3,6 We now examine extracts of neurally derived plasma exosomes from patients with AD, patients with frontotemporal dementia (FTD), and cognitively normal matched controls for differences in quantities of distinct types of lysosome-associated proteins. Results support there being major abnormalities of neural cell autophagic-lysosomal pathways in AD.…”

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

“…Further elaborating on the ESCRT pathway, the endosomal sorting complexes required for transport (ESCRT) is actually composed of four sets of machinery referred to as ESCRT 0, I, ESCRT II, and ESCRT III (Urbanelli et al, 2013). ESCRT 0 recognizes ubiquinated proteins and recruits them for endosomal sorting through interaction of its ubiquitin-binding Hrs FYVE domain with phosphatidyl inositol 3-phosphate (PI3P) (Henne et al, 2011).…”