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ELVs are 100\u00a0nm diameter membrane vesicles shed into the urine by the cells lining the nephron. Using MS\/MS analysis of ELVs from individuals with <jats:italic>PKD1<\/jats:italic> mutations and controls, we show that in addition to the well-described GPS\/GAIN cleavage event in PC1 at 3048 aa and the proprotein convertase cleavage (PPC) event in fibrocystin at 3616 aa, there are multiple other cleavage events in these proteins. The C\u2013terminal 11 transmembrane portion of PC1 undergoes three cleavage events <jats:italic>in vivo<\/jats:italic>. The absence of peptides from the C\u2013terminal cytoplasmic tail of fibrocystin implies a cleavage event close to its single TM domain prior to loading onto the ELVs. There is also evidence that the C\u2013terminal tail of PC2 is also cleaved in ELVs. Native gel analysis of the PCC shows that the entire complex is \u00a0&gt;\u00a02\u00a0MDa in size and that N\u2013terminal GPS\/GAIN cleaved PC1 and PPC cleaved fibrocystin ectodomains can be released under non-reducing conditions and resolve at 300\u00a0kDa. This paper shows that the three major human cystogene proteins are detectable in human urinary ELVs and that all three undergo post-translational proteolytic processing. Human urinary ELVs may be a useful source of material in the search for proteins that interact with the PCC.<\/jats:p>","DOI":"10.1038\/s41598-020-58087-3","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T11:02:57Z","timestamp":1580382177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Analysis of the polycystin complex (PCC) in human urinary exosome\u2013like vesicles (ELVs)"],"prefix":"10.1038","volume":"10","author":[{"given":"Wendy A.","family":"Lea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"McGreal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhulika","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Parnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesya","family":"Zelenchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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