bEndocytosis is an essential process in nearly all eukaryotic cells, including the African trypanosome Trypanosoma brucei. Endocytosis in these organisms is exclusively clathrin mediated, although several lineage-specific features indicate that precise mechanisms are distinct from those of higher eukaryotes. T. brucei Rab21 is a member of an ancient, pan-eukaryotic, endocytic Rab clade that is retained by trypanosomes. We show that T. brucei Rab21 (TbRab21) localizes to endosomes, partially colocalizing with TbRab5A, TbRab28, and TbVps23, the latter two being present at late endosomes. TbRab21 expression is essential for cellular proliferation, and its suppression results in a partial block in traffic to the lysosome. RNA interference (RNAi)-mediated knockdown of TbRab21 had no effect on TbRab5A expression or location but did result in decreased in trans expression of ESCRT (trypanosome endosomal sorting complex required for transport) components and TbRab28, while knockdown of ESCRT subunit TbVps23 resulted in decreased TbRab21 expression. These data suggest that TbRab21 acts downstream of TbRab5A and functions in intimate connection with the trypanosome ESCRT system.
Endocytosis is a crucial process in eukaryotic cells. The GTPases Rab 5, 21 and 22 that mediate endocytosis are ancient eukaryotic features and all available evidence suggests retained conserved function. In animals and fungi, these GTPases are regulated in part by proteins possessing Vps9 domains. However, the diversity, evolution and functions of Vps9 proteins beyond animals or fungi are poorly explored. Here we report a comprehensive analysis of the Vps9 family of GTPase regulators, combining molecular evolutionary data with functional characterization in the non‐opisthokont model organism Trypanosoma brucei. At least 3 subfamilies, Alsin, Varp and Rabex5 + GAPVD1, are found across eukaryotes, suggesting that all are ancient features of regulation of endocytic Rab protein function. There are examples of lineage‐specific Vps9 subfamily member expansions and novel domain combinations, suggesting diversity in precise regulatory mechanisms between individual lineages. Characterization of the Rabex5 + GAPVD1 and Alsin orthologues in T. brucei demonstrates that both proteins are involved in endocytosis, and that simultaneous knockdown prevents membrane recruitment of Rab5 and Rab21, indicating conservation of function. These data demonstrate that, for the Vps9‐domain family at least, modulation of Rab function is mediated by evolutionarily conserved protein‐protein interactions.
Rapid advances in medicine and biotechnology resulted in the development of non-invasive diagnostic and prognostic biomarkers enabling convenient and accurate detection. Exosomes has recently emerged as non-invasive biomarker for a number of diseases including cancer. Exosomes are the small endosome originated membranous vesicles secreted in a number of biological fluids such as serum, saliva, urine, ascites, cerebrospinal fluid, etc. Exosomes contain microRNA proteins and mRNA which can be used as disease specific biomarkers. Here we reviewed recent advancement in the field of exosomes as diagnostic biomarker for cancer along with a brief overview of their biogenesis, function and isolation.
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