RhoB controls the Rab11-mediated recycling and surface reappearance of LFA-1 in migrating T lymphocytes

Abstract

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.

Mammalian Amoeboid Swimming is propelled by molecular and not protrusion-based paddling in Lymphocytes

“…To get further insight into the exact traffic properties of non-actin-bound proteins, it is however interesting to consider that a sustainable axisymmetric retrograde flow of material at cell membrane must topologically be coupled to an internal anterograde flow. Mechanism of internal integrins recycling by anterograde vesicular transport have recently been documented in the literature 35–38 , albeit not for leukocytes nor LFA-1. FRAP experiments on cell front revealed indeed a source of unbleached LFA-1 integrins at the cell leading edge (Figure 7-A and Suppl.…”

CXCR3 regulates CD4+ T cell cardiotropism in pressure overload–induced cardiac dysfunction

“…One possibility is that continuous chemokine signaling during cardiac pressure overload results in transcriptional and/or posttranscriptional regulation of the 2 components of LFA-1 (CD11a and CD18), as previously reported during monocyte differentiation (44). An alternative possibility is that signaling through CXCR3 results in LFA-1 translocation from an intercellular pool to the cell surface, as recently described for T cells during antigen presentation (45) and during T cell migration (46). All of these mechanisms could be in place to enhance LFA-1 presence at the CD4 + T cell surface and increase the chances of LFA-1 activation when CXCL9 and/or CXCL10 chemokines are encountered by CXCR3, resulting in adhesion to intramyocardial ICAM-1 and recruitment into the heart.…”

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

“…Further, Mst1 also activated Myosin IIa which contributed to LFA-1 relocalization in migrating T cells as well [99]. Vesicular transport of LFA-1 from the rear to the cell front was reported to require activity of the small GTPase RhoB, which in turn activated Rab11 [100]. The latter is located in recycling endosomes and controls recycling of endocytosed proteins [101].…”