{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:52:03Z","timestamp":1779889923065,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,7]]},"group-title":"Biochemistry","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R35GM143050"],"award-info":[{"award-number":["R35GM143050"]}]},{"name":"NIH","award":["R01GM120137"],"award-info":[{"award-number":["R01GM120137"]}]},{"name":"NIH","award":["R01HL123078"],"award-info":[{"award-number":["R01HL123078"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The actin cytoskeleton drives essential processes like cell migration and muscle contraction. While barbed-end polymerization is well-established, pointed-end elongation was long considered impossible\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Here, we demonstrate that Leiomodin 2 (Lmod2), which localizes to thin-filament pointed ends (PEs) in striated muscle cells, functions as the first identified eukaryotic processive actin polymerase. Single-molecule and single-filament imaging reveal that Lmod2 stably associates with PEs\n                  <jats:italic>in vitro<\/jats:italic>\n                  , enabling elongation even in the presence of high profilin concentrations found in the cytoplasm that otherwise would cause depolymerization of free PEs. We find that both processivity and elongation rate of Lmod are dependent on its WH2 domain. Remarkably, human dilated cardiomyopathy-associated mutations in Lmod2 greatly reduce Lmod2\u2019s PE elongation activity, providing a potential mechanism for disease progression, underscoring the essential role of its actin polymerase activity in formation and maintenance of muscle sarcomeres.\n                <\/jats:p>","DOI":"10.64898\/2026.05.04.720848","type":"posted-content","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:10:28Z","timestamp":1778217028000},"source":"Crossref","is-referenced-by-count":1,"title":["Leiomodin 2 functions as a processive pointed-end elongator of actin filaments"],"prefix":"10.64898","author":[{"given":"Sudipta","family":"Biswas","sequence":"first","affiliation":[{"name":"Departments of Physics, Biochemistry and Cell Biology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania M.","family":"Larrinaga","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Medicine and Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Choubey","sequence":"additional","affiliation":[{"name":"The Institute of Mathematical Sciences, Chennai 600113, India"},{"name":"Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol C.","family":"Gregorio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-0151","authenticated-orcid":false,"given":"Shashank","family":"Shekhar","sequence":"additional","affiliation":[{"name":"Departments of Physics, Biochemistry and Cell Biology, Emory University, Atlanta, GA 30322, 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