{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:47:11Z","timestamp":1790437631704,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,12]],"date-time":"2020-01-12T00:00:00Z","timestamp":1578787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["480\/12\u20101"],"award-info":[{"award-number":["480\/12\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>BEST1<\/jats:italic>\n                    gene product bestrophin\u20101, a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010dependent anion channel, interacts with Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels in the retinal pigment epithelium (RPE).\n                    <jats:italic>BEST1<\/jats:italic>\n                    mutations lead to Best vitelliform macular dystrophy. A common functional defect of these mutations is reduced trafficking of bestrophin\u20101 into the plasma membrane. We hypothesized that this defect affects the interaction partner Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 channel affecting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and altered RPE function. Thus, we investigated the protein interaction between Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 channels and bestrophin\u20101 by immunoprecipitation, Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 activity in the presence of mutant bestrophin\u20101 and intracellular trafficking of the interaction partners in confluent RPE monolayers. We selected four\n                    <jats:italic>BEST1<\/jats:italic>\n                    mutations, each representing one mutational hotspot of the disease: T6P, F80L, R218C, and F305S. Heterologously expressed L\u2010type channels and mutant bestrophin\u20101 showed reduced interaction, reduced Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 channel activity, and changes in surface expression. Transfection of polarized RPE (porcine primary cells, iPSC\u2010RPE) that endogenously express Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 and wild\u2010type bestrophin\u20101, with mutant bestrophin\u20101 confirmed reduction of Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 surface expression. For the four selected\n                    <jats:italic>BEST1<\/jats:italic>\n                    mutations, presence of mutant bestrophin\u20101 led to reduced Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 activity by modulating pore\u2010function or decreasing surface expression. Reduced Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.3 activity might open new ways to understand symptoms of Best vitelliform macular dystrophy such as reduced electro\u2010oculogram, lipofuscin accumulation, and vision impairment.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901202rr","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T02:05:10Z","timestamp":1578881110000},"page":"4055-4071","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Ca\n                    <sup>2+<\/sup>\n                    channel surface expression by mutant bestrophin\u20101 in RPE cells"],"prefix":"10.1096","volume":"34","author":[{"given":"Magdalena","family":"Cordes","sequence":"first","affiliation":[{"name":"Experimental Ophthalmology Department of Ophthalmology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin a corporate member of Freie Universit\u00e4t Humboldt\u2010University the Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Bucichowski","sequence":"additional","affiliation":[{"name":"Experimental Ophthalmology Department of Ophthalmology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin a corporate member of Freie Universit\u00e4t Humboldt\u2010University the Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad S.","family":"Alfaar","sequence":"additional","affiliation":[{"name":"Experimental Ophthalmology Department of Ophthalmology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin a corporate member of Freie Universit\u00e4t Humboldt\u2010University the Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Jonas Children's Vision Care, and Bernard &amp; Shirlee Brown Glaucoma Laboratory Department of Ophthalmology Columbia Stem Cell Initiative Departments of Ophthalmology Pathology &amp; Cell Biology Institute of Human Nutrition College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Edward S. Harkness Eye Institute New York\u2010Presbyterian Hospital New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seba","family":"Almedawar","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Bioengineering (CMCB) Center for Regenerative Therapies, Dresden (CRTD) Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Reichhart","sequence":"additional","affiliation":[{"name":"Experimental Ophthalmology Department of Ophthalmology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin a corporate member of Freie Universit\u00e4t Humboldt\u2010University the Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Strau\u00df","sequence":"additional","affiliation":[{"name":"Experimental Ophthalmology Department of Ophthalmology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin a corporate member of Freie Universit\u00e4t Humboldt\u2010University the Berlin Institute of Health Berlin 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