{"doi":"10.1083/jcb.201501038","title":"PtdIns(4,5)P2 and PtdIns3P coordinate to regulate phagosomal sealing for apoptotic cell clearance","abstract":"<jats:p>Phagocytosis requires phosphoinositides (PIs) as both signaling molecules and localization cues. How PIs coordinate to control phagosomal sealing and the accompanying switch of organelle identity is unclear. In this study, we followed dynamic changes in PIs during apoptotic cell clearance in Caenorhabditis elegans. We found that phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3-phosphate (PtdIns3P), which accumulate transiently on unsealed and fully sealed phagosomes, respectively, are both involved in phagosome closure. We identified PtdIns3P phosphatase MTM-1 as an effector of PtdIns(4,5)P2 to promote phagosomal sealing. MTM-1 coordinates with the class II PI3 kinase PIKI-1 to control PtdIns3P levels on unsealed phagosomes. The SNX9 family protein LST-4 is required for sealing, and its association with unsealed phagosomes is regulated by PtdIns(4,5)P2, PIKI-1, and MTM-1. Loss of LST-4 or its retention on phagosomes disrupts sealing and suppresses PtdIns3P accumulation, indicating close coupling of the two events. Our findings support a coincidence detection mechanism by which phagosomal sealing is regulated and coupled with conversion from PtdIns(4,5)P2 enrichment on unsealed phagosomes to PtdIns3P enrichment on fully sealed phagosomes.</jats:p>","journal":"Journal of Cell Biology","year":2015,"id":666684,"datarank":0.6190701577567639,"base_score":4.127134385045092,"endowment":4.127134385045092,"self_citation_contribution":0.6190701577567639,"citation_network_contribution":0.0,"self_endowment_contribution":0.6190701577567639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":61,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":218516,"name":"Kun Wang","orcid":"0000-0002-9533-7452","position":1,"is_corresponding":false},{"id":1074478,"name":"Wei Zou","orcid":"0000-0001-8292-5127","position":2,"is_corresponding":false},{"id":863695,"name":"Rui Miao","orcid":"0000-0002-5541-3852","position":3,"is_corresponding":false},{"id":1741039,"name":"Yaling Huang","orcid":null,"position":4,"is_corresponding":false},{"id":146273,"name":"Haibin Wang","orcid":null,"position":5,"is_corresponding":false},{"id":1326829,"name":"Xiaochen Wang","orcid":"0000-0001-9412-0596","position":6,"is_corresponding":false},{"id":1201566,"name":"Shiya Cheng","orcid":"0000-0001-8643-8748","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"PtdIns(4,5)P2 and PtdIns3P coordinate to regulate phagosomal sealing for apoptotic cell clearance","abstract":"<jats:p>Phagocytosis requires phosphoinositides (PIs) as both signaling molecules and localization cues. How PIs coordinate to control phagosomal sealing and the accompanying switch of organelle identity is unclear. In this study, we followed dynamic changes in PIs during apoptotic cell clearance in Caenorhabditis elegans. We found that phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3-phosphate (PtdIns3P), which accumulate transiently on unsealed and fully sealed phagosomes, respectively, are both involved in phagosome closure. We identified PtdIns3P phosphatase MTM-1 as an effector of PtdIns(4,5)P2 to promote phagosomal sealing. MTM-1 coordinates with the class II PI3 kinase PIKI-1 to control PtdIns3P levels on unsealed phagosomes. The SNX9 family protein LST-4 is required for sealing, and its association with unsealed phagosomes is regulated by PtdIns(4,5)P2, PIKI-1, and MTM-1. Loss of LST-4 or its retention on phagosomes disrupts sealing and suppresses PtdIns3P accumulation, indicating close coupling of the two events. Our findings support a coincidence detection mechanism by which phagosomal sealing is regulated and coupled with conversion from PtdIns(4,5)P2 enrichment on unsealed phagosomes to PtdIns3P enrichment on fully sealed phagosomes.</jats:p>","is_dataset_classified":null,"base_score":4.127134385045092,"endowment":4.127134385045092,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26240185","pmcid":"PMC4523610","openalex_id":"https://openalex.org/W1880487999","authors":[],"funders":[{"funder_name":"NIH HHS","grant_id":"P40OD010440","title":null},{"funder_name":"National Institutes of Health","grant_id":"1P40OD010440-01","title":"Caenorhabditis Genetics Center"},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":3,"fwci":3.2056,"citation_percentile":0.91712851,"influential_citations":7,"citation_trend":[{"year":2016,"count":8},{"year":2017,"count":5},{"year":2018,"count":9},{"year":2019,"count":4},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2022,"count":2},{"year":2023,"count":10},{"year":2025,"count":12},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by-nc-sa","oa_locations":[{"url":"https://rupress.org/jcb/article-pdf/210/3/485/952282/jcb_201501038.pdf","host_type":"journal"},{"url":"https://rupress.org/jcb/article-pdf/210/3/485/952282/jcb_201501038.pdf","host_type":"HYBRID"},{"url":"https://rupress.org/jcb/article-pdf/210/3/485/952282/jcb_201501038.pdf","host_type":"publisher"},{"url":"https://rupress.org/jcb/article-pdf/210/3/485/1592305/jcb_201501038.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1083/jcb.201501038","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26240185","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4523610","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4523610","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4523610?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1083/jcb.201501038","host_type":""},{"url":"https://dx.doi.org/10.1083/jcb.201501038","host_type":""}],"fields_of_study":["Cellular transport and secretion","Phagocytosis and Immune Regulation","Erythrocyte Function and Pathophysiology","Biology","Medicine","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Animals","Cell Line","Humans","Lysosomes","Phagocytosis","Phosphoric Monoester Hydrolases","Caenorhabditis elegans","Apoptosis","Phosphatidylinositol Phosphates","Phosphatidylinositol 4,5-Diphosphate","Phosphatidylinositol 3-Kinases","Caenorhabditis elegans Proteins","RNA Interference","RNA, Small Interfering","HEK293 Cells","Sorting Nexins","Class III Phosphatidylinositol 3-Kinases"],"keywords":["Phagosome","Cell biology","Phagocytosis","Biology","Phosphatidylinositol","Caenorhabditis elegans","Organelle","Autophagy","Signal transduction","Apoptosis","Biochemistry","Research Articles"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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