LAUSR

Imaging analysis reveals a mechanism for the integrin recycling required to maintain T cell migration. Recycling integrins T cells must rapidly migrate along endothelial cell surfaces and transmigrate to reach sites of infection and inflammation in tissues. The cell surface integrin LFA-1 binds to its ligand ICAM-1 on endothelial cells in a dynamic manner so that T cells rapidly adhere to and detach from the endothelial surface to migrate quickly. Using biochemical and imaging analyses, Samuelsson et al. identified a process by which LFA-1, internalized after its interaction with ICAM-1, is recycled back to the T cell surface to maintain migration. LFA-1 bound to the GTPase RhoB in the cytosol, which mediated its recruitment to Rab11-positive rapidly recycling endosomes. Loss of RhoB function resulted in the cytosolic accumulation of LFA-1 at the rear of the cell, reduced cell surface abundance of LFA-1, and impaired T cell migration. The regulation of cell adhesion and motility is complex and requires the intracellular trafficking of integrins to and from sites of cell adhesion, especially in fast-moving cells such as leukocytes. The Rab family of guanosine triphosphatases (GTPases) is essential for vesicle transport, and vesicles mediate intracellular integrin trafficking. We showed that RhoB regulates the vesicular transport of the integrin LFA-1 along the microtubule network in migrating T lymphocytes. Impairment in RhoB function resulted in the accumulation of both LFA-1 and the recycling endosomal marker Rab11 at the rear of migrating T lymphocytes and decreased the association between these molecules. T lymphocytes lacking functional RhoB exhibited impaired recycling and subsequently decreased surface amounts of LFA-1, leading to reduced T cell adhesion and migration mediated by the cell adhesion molecule ICAM-1 (intercellular adhesion molecule–1). We propose that vesicle-associated RhoB is a regulator of the Rab11-mediated recycling of LFA-1 to the cell surface, an event that is necessary for T lymphocyte motility.