PXD073976-1

PXD073976 is an original dataset announced via ProteomeXchange.

Title	Proteasomal dependent disruption of mechanosensors during Leptospira interrogans infection induces aberrant collective cell migration
Description	Leptospira interrogans is the causative agent of leptospirosis, a potentially severe and life-threatening zoonotic infectious disease. One of the symptoms associated with severe leptospirosis is acute kidney failure, with detachment of renal tubule epithelial cells (RPTECs) from the basement membrane, which can develop into chronic kidney disease. The kidney intrinsically possesses the ability to self-repair after acute injury through collective cell migration, which involves the movement of cells as a cohesive unit. L. interrogans induces the disassembly of adherens junctions, which can be prevented by inhibitors of the eukaryotic proteolytic pathways. However, the impact on epithelial repair processes have not been investigated yet. In this study, we performed a proteome-wide analysis of protein ubiquitination in infected-RPTECs and identified ARL2, a protein involved in microtubule dynamics. Immunofluorescence analysis showed that L. interrogans induces a proteasomal-dependent disruption of the microtubule/F-actin cytoskeletal network. Consequently, an aberrant collective cell migration was observed in a scratch assay, which was improved by proteasomal inhibition. Our data suggested that L. interrogans alters a circuit integrating mechanosensors at cell–cell contacts and the supracellular F-actin/microtubule cytoskeleton network. Proteasome inhibition prevents the disruption of this circuit and might improve RPTECs' repair responses. Our findings emphasize the role of the Ubiquitinin Proteasome System in leptospiral pathogenesis as the basis for novel treatment strategies to prevent renal damage.
HostingRepository	jPOST
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-15_08:00:30.629.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; ubiquitinylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-02 20:48:09	ID requested
⏵ 1	2026-03-15 08:00:31	announced

Dataset with its publication pending

submitter keyword: Leptospira interrogans, renal tubule epithelial cells, mechanosensors, F-actin, microtubule

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

jPOST dataset URI

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