{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:47:22Z","timestamp":1792036042340,"version":"4.4.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,2,5]]},"abstract":"<jats:p>\n                    Bone remodeling requires osteoclasts to generate and maintain an acidified resorption compartment between the apical membrane and the bone surface to solubilize hydroxyapatite crystals within the bone matrix. This acidification process requires (\n                    <jats:italic>i<\/jats:italic>\n                    ) apical proton secretion by a vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase, (\n                    <jats:italic>ii<\/jats:italic>\n                    ) actin cytoskeleton reorganization into a podosome belt that forms a gasket to restrict lacunar acid leakage, and (\n                    <jats:italic>iii<\/jats:italic>\n                    ) basolateral chloride uptake and bicarbonate extrusion by an anion exchanger to provide Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    permissive for apical acid secretion while preventing cytoplasmic alkalinization. Here we show that osteoclast-targeted deletion in mice of solute carrier family 4 anion exchanger member 2 (\n                    <jats:italic>Slc4a2<\/jats:italic>\n                    ) results in osteopetrosis. We further demonstrate a previously unrecognized consequence of SLC4A2 loss of function in the osteoclast: dysregulation of calpain-dependent podosome disassembly, leading to abnormal actin belt formation, cell spreading, and migration. Rescue of SLC4A2-deficient osteoclasts with functionally defined mutants of SLC4A2 indicates regulation of actin cytoskeletal reorganization by anion-exchange activity and intracellular pH, independent of SLC4A2\u2019s long N-terminal cytoplasmic domain. These data suggest that maintenance of intracellular pH in osteoclasts through anion exchange regulates the actin superstructures required for bone resorption.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1206392110","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:27:25Z","timestamp":1358908045000},"page":"2163-2168","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["SLC4A2-mediated Cl\n                    <sup>\u2212<\/sup>\n                    \/HCO\n                    <sub>3<\/sub>\n                    <sup>\u2212<\/sup>\n                    exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts"],"prefix":"10.1073","volume":"110","author":[{"given":"Fabienne","family":"Coury","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serhan","family":"Zenger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew K.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Renal Division and Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, 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and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth L.","family":"Alper","sequence":"additional","affiliation":[{"name":"Renal Division and Molecular and Vascular Medicine Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios O.","family":"Aliprantis","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115;"},{"name":"Division of Rheumatology, Department of Medicine, Brigham and 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