biostudies-literatureLea WANIDDK NIH HHS1500https://www.ebi.ac.uk/biostudies/studies/S-EPMC6992733biostudies-literatureUnknown10(1)The polycystin-1 (PC1), polycystin-2 (PC2) and fibrocystin proteins, the respective products of the PKD1, PKD2 and PKHD1 genes, are abundant in urinary exosome-like vesicles (ELVs) where they form the polycystin complex (PCC). ELVs are 100 nm diameter membrane vesicles shed into the urine by the cells lining the nephron. Using MS/MS analysis of ELVs from individuals with PKD1 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-terminal 11 transmembrane portion of PC1 undergoes three cleavage events in vivo. The absence of peptides from the C-terminal cytoplasmic tail of fibrocystin implieScientific reportsAnalysis of the polycystin complex (PCC) in human urinary exosome-like vesicles (ELVs).PMC6992733P30 DK090868P30 DK106912RC1 DK086161R01 DK080688Johnson KLMcCormick DJZelenchuk LMcGreal KWard CJMadden BJParnell SCCharlesworth MCHogan MCLea WASharma MfalseAnalysis of the polycystin complex (PCC) in human urinary exosome-like vesicles (ELVs).The polycystin-1 (PC1), polycystin-2 (PC2) and fibrocystin proteins, the respective products of the PKD1, PKD2 and PKHD1 genes, are abundant in urinary exosome-like vesicles (ELVs) where they form the polycystin complex (PCC). ELVs are 100 nm diameter membrane vesicles shed into the urine by the cells lining the nephron. Using MS/MS analysis of ELVs from individuals with PKD1 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-terminal 11 transmembrane portion of PC1 undergoes three cleavage events in vivo. The absence of peptides from the C-terminal cytoplasmic tail of fibrocystin implie2020-01-01T00:00:00Z2020 Jan2026-05-07T21:53:31.498Z2020-05-22T09:29:22ZS-EPMC69927333200176810.1038/s41598-020-58087-3