Journal Article

FZJ-2017-07844

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte Cytoskeleton

Rinschen, M. M. (Corresponding author) ; Hoppe, A.-K. ; Grahammer, F. ; Kann, M. ; Völker, L. A. ; Schurek, E.-M. ; Binz, J. ; Höhne, M. ; Demir, F.FZJ* ; Malisic, M. ; Huber, T. B. ; Kurschat, C. ; Kizhakkedathu, J. N. ; Schermer, B. ; Huesgen, P.FZJ* ; Benzing, T.

2017
American Society of Nephrology Washington, DC

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/17598  doi:10.1681/ASN.2016101119

Abstract: Regulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo. We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin. Quantitative mapping of N-termini demonstrated perturbation of protease action during podocyte injury in vitro, including diminished proteolysis of α-actinin-4. Differentially regulated protease substrates comprised cytoskeletal proteins as well as intermediate filaments. Determination of preferential protease motifs during podocyte damage indicated activation of caspase proteases and inhibition of arginine-specific proteases. Several proteolytic processes were clearly site-specific, were conserved across species, and could be confirmed by differential migration behavior of protein fragments in gel electrophoresis. Some of the proteolytic changes discovered in vitro also occurred in two in vivo models of podocyte damage (WT1 heterozygous knockout mice and puromycin aminonucleoside–treated rats). Thus, we provide direct and systems-level evidence that the slit diaphragm and podocyte cytoskeleton are regulated targets of proteolytic modification, which is altered upon podocyte damage.

---

Contributing Institute(s):

1. Analytik (ZEA-3)

Research Program(s):

1. 582 - Plant Science (POF3-582) (POF3-582)

Appears in the scientific report 2017

---

Database coverage:
; ; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---