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Persistent DRM association is required for recycling of the internalized receptor because 1) &gt;90% of endocytosed LFA-1 is associated with DRM, and a large fraction of the internalized receptor colocalizes intracellularly with markers of DRM and the recycling endocytic compartment; 2) a recycling-defective mutant (\u03b1L\/\u03b2<jats:sub>2<\/jats:sub><jats:sup>Y735A<\/jats:sup>) dissociates rapidly from DRM upon being endocytosed and is subsequently diverted into a late endosomal pathway; and 3) a dominant negative Rab11 mutant (Rab11<jats:sup>S25N<\/jats:sup>) induces intracellular accumulation of endocytosed \u03b1L\/\u03b2<jats:sub>2<\/jats:sub>and prevents its enrichment in chemoattractant-induced lamellipodia. Notably, chemokine-induced migration of neutrophils over immobilized ICAM-1 is abrogated by cholesterol-sequestering agents. We propose that DRM-associated endocytosis allows efficient retrieval of integrins, as they detach from their ligands, followed by polarized recycling to areas of the plasma membrane, such as lamellipodia, where they establish new adhesive interactions and promote outside-in signaling events.<\/jats:p>","DOI":"10.1091\/mbc.e05-05-0413","type":"journal-article","created":{"date-parts":[[2005,10,6]],"date-time":"2005-10-06T00:33:17Z","timestamp":1128558797000},"page":"5793-5803","source":"Crossref","is-referenced-by-count":108,"title":["Dynamic Partitioning into Lipid Rafts Controls the Endo-Exocytic Cycle of the \u03b1L\/\u03b2<sub>2<\/sub>Integrin, LFA-1, during Leukocyte Chemotaxis"],"prefix":"10.1091","volume":"16","author":[{"given":"Monica","family":"Fabbri","sequence":"first","affiliation":[{"name":"Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of Medicine, DIBIT-Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Meglio","sequence":"additional","affiliation":[{"name":"Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of Medicine, DIBIT-Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Gagliani","sequence":"additional","affiliation":[{"name":"MicroSCoBiO Research Center and IFOM Center of Cell Oncology and Ultrastructure, Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Consonni","sequence":"additional","affiliation":[{"name":"Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of Medicine, DIBIT-Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Molteni","sequence":"additional","affiliation":[{"name":"Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of Medicine, DIBIT-Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Bender","sequence":"additional","affiliation":[{"name":"Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Sections of Cardiovascular Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT 06536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Tacchetti","sequence":"additional","affiliation":[{"name":"MicroSCoBiO Research Center and IFOM Center of Cell Oncology and Ultrastructure, Department of Experimental Medicine, University of Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruggero","family":"Pardi","sequence":"additional","affiliation":[{"name":"Unit of Leukocyte Biology, Vita-Salute San Raffaele University School of Medicine, DIBIT-Scientific Institute San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Beardsley, A., Fang, K., Mertz, H., Castranova, V., Friend, S., and Liu, J. 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