Dynamic Partitioning into Lipid Rafts Controls the Endo-Exocytic Cycle of the αL/β2Integrin, LFA-1, during Leukocyte Chemotaxis

Autor: Monica Fabbri, Raffaella Molteni, Maria Cristina Gagliani, Carlo Tacchetti, Ruggero Pardi, Silvia Di Meglio, Jeffrey R. Bender, Elisa Consonni
Rok vydání: 2005
Předmět:
Zdroj: Molecular Biology of the Cell. 16:5793-5803
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.e05-05-0413
Popis: Cell migration entails the dynamic redistribution of adhesion receptors from the cell rear toward the cell front, where they form new protrusions and adhesions. This process may involve regulated endo-exocytosis of integrins. Here we show that in primary neutrophils unengaged αL/β2integrin (LFA-1) is internalized and rapidly recycled upon chemoattractant stimulation via a clathrin-independent, cholesterol-sensitive pathway involving dynamic partitioning into detergent-resistant membranes (DRM). Persistent DRM association is required for recycling of the internalized receptor because 1) >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 (αL/β2Y735A) dissociates rapidly from DRM upon being endocytosed and is subsequently diverted into a late endosomal pathway; and 3) a dominant negative Rab11 mutant (Rab11S25N) induces intracellular accumulation of endocytosed αL/β2and 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.
Databáze: OpenAIRE
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