PXD040838

PXD040838 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Leptospira interrogansinduces the degradation of E-cadherin scaffolding proteins p0071 and p120-catenin to disrupt the junctional complex
Description	Leptospira interrogans disseminates hematogenously to reach the target organs by disrupting the epithelial junctional complexes (JCs). We have previously demonstrated that transmigration of L. interrogansacross polarized renal proximal tubule epithelial cells (RPTECs) induces E-cadherin (E-cad) endocytosis, mislocalization of JC proteins and cytoskeletal rearrangement without significant changes in the transcript levels of JC-associated proteins. Here, we use a combination of proteomic and imaging analysis with chemical inhibition studies to demonstrate that L. interrogansco-opts host protein degradation pathways to target scaffolding proteins, p0071 and p120-catenin, which stabilize E-cad at the plasma membrane. L. interrogans-induced decrease of RPTECs transepithelial electrical resistance can be totally mitigated by the proteasomal inhibitors MG-132 or bortezomib, or partially prevented by the pan-caspase inhibitor Z-VAD-FMK. Furthermore, the combination of MG-132 with the lysosomal inhibitor bafilomycin significantly prevent p120-catenin degradation and its displacement from the JC without preventing p0071 proteolysis. The degradation and displacement of p0071 from the JC was inhibited by Z-VAD-FMK. These results demonstrate that p120-catenin and p0071 have redundant roles as proteins stabilizing E-cad at the JC of RPTECs. L. interrogans induces the degradation of both proteins by multiple pathways to efficiently destroy the monolayer integrity.
HostingRepository	jPOST
AnnounceDate	2023-08-31
AnnouncementXML	Submission_2023-08-30_17:53:54.719.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hidenori Yamanaka
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; deamidated L-glutamine; deamidated L-asparagine
Instrument	Q Exactive

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-13 19:20:43	ID requested
⏵ 1	2023-08-30 17:53:55	announced

Publication List

Dataset with its publication pending

Dataset with its publication pending

Keyword List

submitter keyword: Leptospira interrogans, renal proximal tubule epithelial cells, junctional complex, p120-catenin, p0071 (plakophilin-4)

submitter keyword: Leptospira interrogans, renal proximal tubule epithelial cells, junctional complex, p120-catenin, p0071 (plakophilin-4)

Contact List

Claudia Toma
lab head
Hidenori Yamanaka
contact affiliation	Chemicals Evaluation and Research Institute
dataset submitter

Full Dataset Link List

jPOST dataset URI
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jPOST dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST002081/