PXD054444-1
PXD054444 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | The C. elegans PTPN22 ortholog functions in diverse developmental processes |
Description | Non-receptor type protein tyrosine phosphatases (PTPNs) have been studied extensively in the context of the adaptive immune system, however, their roles beyond immunoregulation are less unexplored. Here we identify novel functions for the conserved C. elegans phosphatase, PTPN-22, establishing new links to worm molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen, we found that loss of PTPN-22 phosphatase activity suppresses molting defects caused by loss-of-function mutations in the conserved NIMA-related kinases, NEKL-2 (human NEK8/9) and NEKL-3 (human NEK6/7), which act at the interface of membrane trafficking and actin regulation. To better understand the functions of PTPN-22 we carried out proximity labeling studies to identify candidate interactors of PTPN-22 during development. Through this approach we identified the CDC42 guanine-nucleotide exchange factor DNBP-1 (human DNMBP) as an in vivo partner of PTPN-22 and showed that loss of DNBP-1 also suppresses nekl-associated molting defects and partially co-localizes with PTPN-22 in the epidermis. Genetics analysis, co-localization studies, and proximity labeling also revealed roles for PTPN-22 in several epidermal adhesion complexes including C. elegans hemidesmosomes, suggesting that PTPN-22 plays a broad role in maintaining the structural integrity of tissues. Localization and proximity labeling also implicated PTPN-22 in functions connected to nucleocytoplasmic transport and mRNA regulation, particularly within the germline, as nearly one third of proteins identified by PTPN-22 proximity labeling are known P granule components. Collectively, our studies highlight the utility of combined genetic and proteomic approaches for identifying novel gene functions. |
HostingRepository | MassIVE |
AnnounceDate | 2024-08-12 |
AnnouncementXML | Submission_2024-08-12_07:30:51.302.xml |
DigitalObjectIdentifier | |
ReviewLevel | Non peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Stephanie Byrum |
SpeciesList | scientific name: Caenorhabditis elegans; common name: roundworm; NCBI TaxID: 6239; |
ModificationList | Oxidation |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-07-31 07:19:06 | ID requested | |
⏵ 1 | 2024-08-12 07:30:51 | announced |
Publication List
no publication |
Keyword List
submitter keyword: C. elegans, Tyrosine Phosphatase, TurboID, proximity-dependent protein labeling |
Contact List
David S. Fay | |
---|---|
contact affiliation | University of Wyoming |
contact email | DavidFay@uwyo.edu |
lab head | |
Stephanie Byrum | |
contact affiliation | University of Arkansas for Medical Sciences |
contact email | sbyrum@uams.edu |
dataset submitter |
Full Dataset Link List
MassIVE 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://massive.ucsd.edu/v08/MSV000095492/ |