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

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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 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. 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. All MS data have been deposited in the ProteomeXchange with identifier PXD001005 (http://proteomecentral.proteomexchange.org/dataset/PXD001005).", "claims": [{"id": "claim-target-result", "statement": "Cross-species comparison of glomerular phosphoproteomic data revealed biologically relevant conserved phosphorylation events and showed that podocin phosphorylation regulates its interaction with nephrin and CD2AP; the underlying MS data are publicly available through ProteomeXchange under identifier PXD001005.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25420462", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here, we present the result of phosphoproteomic analyses of cow and rat glomeruli to allow cross-species comparisons."}, {"asset": "source:pmid:25420462", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}, {"asset": "source:pmid:25420462", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We studied a highly conserved podocin phosphorylation site in greater detail and show that phosphorylation regulates affinity of the interaction with nephrin and CD2AP."}, {"asset": "source:pmid:25420462", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "All MS data have been deposited in the ProteomeXchange with identifier PXD001005 (http://proteomecentral.proteomexchange.org/dataset/PXD001005)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Cross-species comparison of glomerular phosphoproteomic data revealed biologically relevant conserved phosphorylation events and showed that podocin phosphorylation regulates its interaction with nephrin and CD2AP; the underlying MS data are publicly available through ProteomeXchange under identifier PXD001005.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25420462"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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