{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qi Y"],"funding":["Research Grants Council, University Grants Committee"],"pagination":["127"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11933580"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["82(1)"],"pubmed_abstract":["Podosomes are adhesion structures with densely-polymerized F-actin. While PI(3,4,5)P3 and Cdc42-GTP are known factors to trigger WASP-mediated actin polymerization at the macrophage podosome, their causal mechanism to activate WASP remains unclear. Here, we demonstrate that spatially elevated Cdc42-GTP is a downstream effector of local PI(3,4,5)P3 production at the podosome. We further examine the expression and distribution of 19 Cdc42 guanine exchange factors (GEFs) and identify VAV1 as the key PI(3,4,5)P3-dependent Cdc42 GEF. VAV1 is spatially enriched at the macrophage podosome, and the association of VAV1 with the membrane plays a critical role in upregulating its GEF activity. Reintroduction of wildtype VAV1, rather than the PI(3,4,5)P3-binding deficient or catalytically dead mutants"],"journal":["Cellular and molecular life sciences : CMLS"],"pubmed_title":["PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly."],"pmcid":["PMC11933580"],"funding_grant_id":["CRF C7070-22EF","GRF 17121022"],"pubmed_authors":["Yu CH","Qi Y"],"additional_accession":[]},"is_claimable":false,"name":"PI(3,4,5)P3-mediated Cdc42 activation regulates macrophage podosome assembly.","description":"Podosomes are adhesion structures with densely-polymerized F-actin. While PI(3,4,5)P3 and Cdc42-GTP are known factors to trigger WASP-mediated actin polymerization at the macrophage podosome, their causal mechanism to activate WASP remains unclear. Here, we demonstrate that spatially elevated Cdc42-GTP is a downstream effector of local PI(3,4,5)P3 production at the podosome. We further examine the expression and distribution of 19 Cdc42 guanine exchange factors (GEFs) and identify VAV1 as the key PI(3,4,5)P3-dependent Cdc42 GEF. VAV1 is spatially enriched at the macrophage podosome, and the association of VAV1 with the membrane plays a critical role in upregulating its GEF activity. Reintroduction of wildtype VAV1, rather than the PI(3,4,5)P3-binding deficient or catalytically dead mutants","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-07-09T03:04:49.273Z","creation":"2025-07-09T03:04:49.273Z"},"accession":"S-EPMC11933580","cross_references":{"pubmed":["40126693"],"doi":["10.1007/s00018-025-05664-2"]}}