Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier
METADATA ONLY
Loading...
Author / Producer
Date
2014-07
Publication Type
Journal Article
ETH Bibliography
no
Citations
Altmetric
METADATA ONLY
Data
Rights / License
Abstract
Diseases of the kidney filtration barrier are a leading cause of ESRD. Most disorders affect the podocytes, polarized cells with a limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas of in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified in an unbiased tandem mass spectrometry–based approach. We discovered 2449 phosphorylated proteins corresponding to 4079 identified high-confidence phosphorylated residues and performed a systematic bioinformatics analysis of this dataset. We discovered 146 phosphorylation sites on proteins abundantly expressed in podocytes. The prohibitin homology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), located within a phosphorylation motif that is mutated in human genetic forms of proteinuria. The T234 site resides at the interface of podocin dimers. Free energy calculation through molecular dynamic simulations revealed a role for T234 in regulating podocin dimerization. We show that phosphorylation critically regulates formation of high molecular weight complexes and that this may represent a general principle for the assembly of proteins containing prohibitin homology domains.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
25 (7)
Pages / Article No.
1509 - 1522
Publisher
American Society of Nephrology
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Organisational unit
09758 - Beltrao, Pedro / Beltrao, Pedro