Proteomics

Dataset Information

0

Comparative phosphoproteomic analysis of mammalian renal glomeruli

ABSTRACT: Glomerular biology is dependent on tightly controlled signal transduction networks that control phosphorylation of signaling proteins such as cytoskeletal regulators or slit diaphragm proteins of kidney podocytes. Recent, in-depth analysis of the mouse glomerular phosphoproteome by tandem mass spectrometry confidently identified thousands of phosphorylation sites providing a unique opportunity to study signaling in vivo. However, the multitude of phosphorylated residues demands for additional systems biology approaches to separate physiologically important sites from non-functional phosphorylated residues. Cross-species comparison of phosphorylation events is a powerful mean to functionally prioritize and identify physiologically meaningful phosphorylation sites. Here, we present the result of additional phosphoproteomic analyses of the glomerular phosphoproteome in cow and rat to allow cross-species comparisons. We discovered several phosphorylation sites with potentially high biological relevance, e.g. tyrosine phosphorylation of the cytoskeletal regulator synaptopodin and the slit diaphragm protein neph-1 (Kirrel). Moreover, cross-species comparisons revealed conserved phosphorylation of the slit diaphragm protein nephrin on an acidic cluster at the intracellular terminus and conserved podocin phosphorylation on the very carboxyl terminus of the protein. Given the pivotal role of podocin for glomerular biology we studied a highly conserved podocin phosphorylation site in greater detail and show that phosphorylation regulates affinity of the interaction with nephrin and CD2AP. Taken together, these results suggest that species comparisons of phosphoproteomic data may reveal regulatory principles in glomerular biology.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Rattus Norvegicus (rat) Bos Taurus (bovine)

TISSUE(S): Epithelial Cell, Kidney

SUBMITTER: Markus Rinschen  

LAB HEAD: Markus Rinschen

PROVIDER: PXD001005 | Pride | 2015-01-16

REPOSITORIES: Pride

Json Xml
altmetric image

Publications

Comparative phosphoproteomic analysis of mammalian glomeruli reveals conserved podocin C-terminal phosphorylation as a determinant of slit diaphragm complex architecture.

Rinschen Markus M MM   Pahmeyer Caroline C   Pisitkun Trairak T   Schnell Nicole N   Wu Xiongwu X   Maaß Martina M   Bartram Malte P MP   Lamkemeyer Tobias T   Schermer Bernhard B   Benzing Thomas T   Brinkkoetter Paul T PT  

Proteomics 20150119 7

Glomerular biology is dependent on tightly controlled signal transduction networks that control phosphorylation of signaling proteins such as cytoskeletal regulators or slit diaphragm proteins of kidney podocytes. Cross-species comparison of phosphorylation events is a powerful mean to functionally prioritize and identify physiologically meaningful phosphorylation sites. Here, we present the result of phosphoproteomic analyses of cow and rat glomeruli to allow cross-species comparisons. We disco  ...[more]