Rinschen, Markus M., Wu, Xiongwu, Koenig, Tim, Pisitkun, Trairak ORCID: 0000-0001-6677-2271, Hagmann, Henning, Pahmeyer, Caroline, Lamkemeyer, Tobias, Kohli, Priyanka ORCID: 0000-0002-0651-4008, Schnell, Nicole, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Dryer, Stuart, Brooks, Bernard R., Beltrao, Pedro ORCID: 0000-0002-2724-7703, Krueger, Marcus, Brinkkoetter, Paul T. and Benzing, Thomas (2014). Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier. J. Am. Soc. Nephrol., 25 (7). S. 1509 - 1523. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, XiongwuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pisitkun, TrairakUNSPECIFIEDorcid.org/0000-0001-6677-2271UNSPECIFIED
Hagmann, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pahmeyer, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lamkemeyer, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohli, PriyankaUNSPECIFIEDorcid.org/0000-0002-0651-4008UNSPECIFIED
Schnell, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Dryer, StuartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks, Bernard R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beltrao, PedroUNSPECIFIEDorcid.org/0000-0002-2724-7703UNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinkkoetter, Paul T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-434706
DOI: 10.1681/ASN.2013070760
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 25
Number: 7
Page Range: S. 1509 - 1523
Date: 2014
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PODOCYTE TRPC6 CHANNELS; SLIT-DIAPHRAGM; QUANTITATIVE PHOSPHOPROTEOMICS; SIGNALING PATHWAYS; GLOMERULAR PROTEIN; PHOSPHORYLATION; NEPHRIN; KINASE; NPHS2; GENEMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43470

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