{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:05:47Z","timestamp":1792569947687,"version":"4.5.0"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,1,21]]},"abstract":"<jats:p>Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function\u2013associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.<\/jats:p>","DOI":"10.1084\/jem.20071543","type":"journal-article","created":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T00:46:11Z","timestamp":1200962771000},"page":"195-205","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":140,"title":["Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration"],"prefix":"10.1084","volume":"205","author":[{"given":"Nicole A.","family":"Morin","sequence":"first","affiliation":[{"name":"1Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W.","family":"Oakes","sequence":"additional","affiliation":[{"name":"2Department of Physics, Brown University, Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Min","family":"Hyun","sequence":"additional","affiliation":[{"name":"6Department of Microbiologyand Immunology, David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dooyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"4Department of Chemical Engineering"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. Eugene","family":"Chin","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"King","sequence":"additional","affiliation":[{"name":"5Department of Biomedical Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Springer","sequence":"additional","affiliation":[{"name":"3The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Shimaoka","sequence":"additional","affiliation":[{"name":"3The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay X.","family":"Tang","sequence":"additional","affiliation":[{"name":"2Department of Physics, Brown University, Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Reichner","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Rhode Island Hospital and Brown Medical School, Providence, RI 02903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"6Department of Microbiologyand Immunology, David H. 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