{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:14:07Z","timestamp":1790342047677,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030060"],"award-info":[{"award-number":["82030060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,4,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Remodeling the erythrocyte membrane and skeleton by the malarial parasite\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic \u03b1-spectrin, but not \u03b2-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of\n              <jats:italic>P. falciparum,<\/jats:italic>\n              from the ring to the schizont stage. We further observed an upregulated expression of\n              <jats:italic>P. falciparum<\/jats:italic>\n              phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased \u03b1-spectrin ubiquitination and degradation during\n              <jats:italic>P. falciparum<\/jats:italic>\n              development. We further revealed that inhibition of the activity of PfPI3K impaired\n              <jats:italic>P. falciparum<\/jats:italic>\n              development\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>Plasmodium berghei<\/jats:italic>\n              infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of \u03b1-spectrin during the intraerythrocytic development of\n              <jats:italic>Plasmodium<\/jats:italic>\n              species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic \u03b1-spectrin is selectively degraded after\n              <jats:italic>P. falciparum<\/jats:italic>\n              invasion, while \u03b2-spectrin remained intact. We found that the \u03b1-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by\n              <jats:italic>P. falciparum<\/jats:italic>\n              phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in\n              <jats:italic>P. falciparum<\/jats:italic>\n              -infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03510-23","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:00:56Z","timestamp":1710244856000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["<i>Plasmodium falciparum<\/i>\n            selectively degrades \u03b1-spectrin of infected erythrocytes after invasion"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-6142","authenticated-orcid":false,"given":"Kexin","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"},{"name":"Engineering Research Center of Food Fermentation Technology, College of Food Science, Shenyang Agricultural University, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8645-3566","authenticated-orcid":true,"given":"Qilong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0240-2233","authenticated-orcid":false,"given":"Ning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5580-6324","authenticated-orcid":false,"given":"Yanxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3585-3103","authenticated-orcid":false,"given":"Yuxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2303-6391","authenticated-orcid":false,"given":"Yiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-6142","authenticated-orcid":false,"given":"Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-0098","authenticated-orcid":false,"given":"Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8482-5146","authenticated-orcid":false,"given":"Xiaoyu","family":"Sang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-7435","authenticated-orcid":true,"given":"Qijun","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Infectious Diseases, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China"},{"name":"Research Unit for Pathogenic Mechanisms of Zoonotic Parasites, Chinese Academy of Medical Sciences, Shenyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-157735"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00013-19"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.1997.3886"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(89)90006-3"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2021.07.027"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/311177a0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00792-w"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00779-7"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-034157"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.11.011"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701612200"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01322.x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.15.8928"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21344-8"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2011.010394"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA120.002375"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27262"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14412"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00124-10"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-238972"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom9090395"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062917-011931"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8769"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404936200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2566"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2012.09044.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.030882"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082108"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215596084"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1170\/93"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-021-00043-2"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14387"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2023.02.029"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543780903066798"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412152111"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607315"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021280"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/and.13196"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15062"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201642360"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c20070"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1992.11812694"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S262026"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-2061-7"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03510-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03510-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T13:08:14Z","timestamp":1712754494000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03510-23"}},"subtitle":[],"editor":[{"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,10]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,10]]}},"alternative-id":["10.1128\/mbio.03510-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03510-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,10]]},"assertion":[{"value":"2024-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03510-23"}}