PXD009198

PXD009198 is an original dataset announced via ProteomeXchange.

Title	MC1R stabilize the actin cytoskeleton
Description	Amplification of the Melanocortin-1 Receptor in Nephrotic Syndrome Renders a Good Target for Podocyte Cytoskeleton Stabilization During the last years, several reports have been presented of beneficial effects of ACTH in patients with nephrotic syndrome. Among the known ACTH receptors, the melanocortin-1 receptor (MC1R) has been suggested as the mediator of the ACTH renoprotective effect with the mechanism of action resulting in stabilization of the actin cytoskeleton in podocytes. To understand how melanocortin receptors are regulated in nephrotic syndrome and how they are involved in restoration of filtration barrier function, melanocortin receptor expression was evaluated in patients and in a rat model of nephrotic syndrome in combination with cell culture analysis. Phosphoproteomic mass spectrometry was applied and identified MC1R pathways confirmed using biochemical analysis. We found that glomerular MC1R expression was increased in nephrotic syndrome, both in humans and in a rat model. A MC1R agonist protected podocytes from protamine sulfate induced stress fiber loss with the top ranked phoshoproteomic MC1R activated pathway beeing actin cytoskeleton signaling. Actin stabilization through the MC1R consisted of ERK1/2 dependent phosphorylation and inactivation of EGFR signaling with stabilization of synaptopodin and stress fibers in podocytes. These results further explain how patients with nephrotic syndrome show responsiveness to ACTH treatment by depressing EGFR signaling through activation of the MC1R receptor and as a consequence restore filtration barrier function by stabilizing the podocyte actin cytoskeleton.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_10:34:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carina Sihlbom
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-13 08:17:49	ID requested
⏵ 1	2019-11-12 10:34:49	announced

Bergwall L, Wallentin H, Elvin J, Liu P, Boi R, Sihlbom C, Hayes K, Wright D, Haraldsson B, Nystr, ö, m J, Buvall L, Amplification of the Melanocortin-1 Receptor in Nephrotic Syndrome Identifies a Target for Podocyte Cytoskeleton Stabilization. Sci Rep, 8(1):15731(2018) [pubmed]

curator keyword: Biological

submitter keyword: nephrotic syndrome, glomerula, phosphoproteomics, TMT, LC-MS/MS, podocytes, MC1R

Carina Sihlbom
contact affiliation	Proteomics Core Facility, University of Gothenburg
contact email	carina.sihlbom@gu.se
lab head
Carina Sihlbom
contact affiliation	Proteomics Core Facility / University of Gothenburg
contact email	carina.sihlbom@gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009198
     1. Label: PRIDE project
     2. Name: MC1R stabilize the actin cytoskeleton