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PXD026711 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLow kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones
DescriptionOsteoclasts form special integrin-mediated adhesion structures called sealing zones that enable them to adhere to and resorb bone. Sealing zones consist mainly of densely packed podosomes tightly inter-connected by actin fibers. Their formation requires the presence of the hematopoietic integrin regulator kindlin-3. In the current study, we investigated osteoclasts and their adhesion structures in kindlin-3 hypomorphic mice expressing only 5-10% of kindlin-3. Low kindlin-3 expression reduces integrin activity, results in impaired osteoclast adhesion and signaling, and delays cell spreading. Despite these defects, in vitro generated kindlin-3-hypomorphic osteoclasts arrange their podosomes into adhesion patches and belts, which show abnormal podosome and actin organization. Remarkably, kindlin-3-hypomorphic osteoclasts form sealing zones when cultured on calcified matrix in vitro and on bone surface in vivo. However, functional assays as well as immunohistochemical staining and electron micrographs of bone sections showed that they fail to properly seal the resorption lacunae, which is required for secreted proteases to be able to digest bone matrix. This results in mild osteopetrosis. Our study reveals a new, hitherto understudied function of kindlin-3 as an essential organizer of integrin-mediated adhesion structures, such as sealing zones.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTheresa Bock
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-15 05:45:11ID requested
12021-11-25 08:12:27announced
22021-12-03 04:55:09announced2021-12-03: Updated publication reference for PubMed record(s): 34704600.
Publication List
Klapproth S, Richter K, T, ü, rk C, Bock T, Bromberger T, Dominik J, Huck K, Pfaller K, Hess MW, Reichel CA, Kr, ü, ger M, Nakchbandi IA, Moser M, Low kindlin-3 levels in osteoclasts of kindlin-3 hypomorphic mice result in osteopetrosis due to leaky sealing zones. J Cell Sci, 134(22):(2021) [pubmed]
Keyword List
submitter keyword: Kindlin-3, osteoclast, integrin, podosome, sealing zone, bone resorption
Contact List
Markus Moser
contact affiliationInstitute of Experimental Hematology, School of Medicine, Technische Universität München, Munich, D-81675, Germany; Max-Planck Institute of Biochemistry, D-82152 Martinsried
contact emailm.moser@tum.de
lab head
Theresa Bock
contact affiliationCECAD Research Center, University of Cologne
contact emailtbock2@uni-koeln.de
dataset submitter
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Dataset FTP location
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