{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:17:20Z","timestamp":1790029040682,"version":"4.0.1"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100014206","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2017YFA0504901"],"award-info":[{"award-number":["2017YFA0504901"]}],"id":[{"id":"10.13039\/501100014206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014206","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2018YFA0507900"],"award-info":[{"award-number":["2018YFA0507900"]}],"id":[{"id":"10.13039\/501100014206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U2032122"],"award-info":[{"award-number":["U2032122"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31770779"],"award-info":[{"award-number":["31770779"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20S11900200"],"award-info":[{"award-number":["20S11900200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["AoE-M09-12"],"award-info":[{"award-number":["AoE-M09-12"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["C6004-17G"],"award-info":[{"award-number":["C6004-17G"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002843","name":"Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Slit diaphragms between podocytes play a critical role in maintaining the filtration function in kidney. At each slit diaphragm there is an electron-dense junctional plaque crucial for slit diaphragm integrity and podocyte signal transduction. However, the molecular basis underlying slit diaphragm assembly is not well understood. Here, we demonstrate that MAGI2, a unique MAGUK family scaffold protein at slit diaphragm, can autonomously undergo liquid-liquid phase separation. Multivalent interactions among the MAGI2-Dendrin-CD2AP complex drive the formation of the slit diaphragm condensates at physiologic conditions. The reconstituted slit diaphragm condensates can effectively enrich Nephrin. A nephrotic syndrome\u2013associated mutation of\n                      <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                      interferes with slit diaphragm condensate formation, leading to impaired recruitment of Nephrin. Therefore, the electron-dense slit diaphragm assembly might form via phase separation of the slit diaphragm complex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Slit diaphragm is a specialized adhesion junction between the opposing podocytes, establishing the final filtration barrier to urinary protein loss. At the cytoplasmic insertion site of each slit diaphragm there is an electron-dense and protein-rich cellular compartment that is essential for slit diaphragm integrity and signal transduction. Mutations in genes that encode components of this membrane-less compartment have been associated with glomerular diseases. However, the molecular mechanism governing formation of compartmentalized slit diaphragm assembly remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically investigated the interactions between key components at slit diaphragm, such as MAGI2, Dendrin, and CD2AP, through a combination of biochemical, biophysical, and cell biologic approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We demonstrated that MAGI2, a unique MAGUK family scaffold protein at slit diaphragm, can autonomously undergo liquid-liquid phase separation. Multivalent interactions among the MAGI2-Dendrin-CD2AP complex drive the formation of the highly dense slit diaphragm condensates at physiologic conditions. The reconstituted slit diaphragm condensates can effectively recruit Nephrin. A nephrotic syndrome\u2013associated mutation of\n                      <jats:italic toggle=\"yes\">MAGI2<\/jats:italic>\n                      interfered with formation of the slit diaphragm condensates, thus leading to impaired enrichment of Nephrin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Key components at slit diaphragm (\n                      <jats:italic toggle=\"yes\">e.g.<\/jats:italic>\n                      , MAGI2 and its complex) can spontaneously undergo phase separation. The reconstituted slit diaphragm condensates can be enriched in adhesion molecules and cytoskeletal adaptor proteins. Therefore, the electron-dense slit diaphragm assembly might form via phase separation of core components of the slit diaphragm in podocytes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020111590","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T15:43:42Z","timestamp":1627659822000},"page":"1946-1960","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration Barrier"],"prefix":"10.1681","volume":"32","author":[{"given":"Haijiao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China"},{"name":"School of Life Sciences, Southern University of Science and Technology, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-0143","authenticated-orcid":false,"given":"Jinwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,8]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev-physiol-020911-153238","article-title":"Cell biology and pathology of podocytes","volume":"74","author":"Greka","year":"2012","journal-title":"Annu Rev Physiol"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbrc.2010.04.069","article-title":"Molecular make-up of the glomerular filtration barrier","volume":"396","author":"Patrakka","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B3-20240826","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000481633","article-title":"A review of podocyte biology","volume":"47","author":"Garg","year":"2018","journal-title":"Am J 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