MUC1(insC) affects vesicular transport in renal epithelial cells

ABSTRACT: Autosomal dominant tubulointerstitial kidney disease associated to the MUC1 gene (ADTKD-MUC1; formerly MCKD1) belongs to a heterogenous group of rare hereditary kidney diseases that is prototypically caused by frameshift mutations in the MUC1 repeat domain. The mutant MUC1(insC) lacks the transmembrane domaine, exhibits aberant cellular topology and hence might gain a function during the pathological process. To get insight into potential pathomechanisms we performed differential proteomics of extracellular vesicles shed by renal epithelia into the urine of patients. The study was based on three ADTKD patients and individual controls applying iTRAQ/LC-MS/MS. A total of 727 proteins were identified across all biological and technical replicates. A proportion of 47 proteins (6.5%) were fold-changed species. GO Term Enrichment analysis revealed proteins with significantly changed expression in ADTKD-associated extracellular vesicles as vesicular transport-associated proteins. Among these VTA1 is involved in the multivesicular body (MVB) pathway similar to the charged multivesicular body protein CHMP2B. VTA1 is also claimed to play roles as a cofactor of the AAA ATPases VPS4A and B in the disassembly of ESCRT III. Protein interaction databases list VPS4B, CHMP2A and IST1 as VTA1 binding partners.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Kidney Disease

SUBMITTER: Stefan Mueller  

LAB HEAD: Franz-Georg Hanisch

PROVIDER: PXD008389 | Pride | 2018-02-23

REPOSITORIES: Pride