Regulation of integrins is critical for lymphocyte adhesion to endothelium and trafficking through secondary lymphoid organs. Inside-out signaling to integrins is mediated by the small GTPase Rap1. Two effectors of Rap1 regulate integrins, RapL and Rap1 interacting adaptor molecule (RIAM). Using mice conditionally deficient in both Rap1a and Rap1b and mice null for RIAM, we show that the Rap1/R...

Cell migration and invasion require regulated turnover of integrin-dependent adhesion complexes. Rap1-GTP-interacting adaptor molecule (RIAM) is an adaptor protein that mediates talin recruitment to the cell membrane, and whose depletion leads to defective melanoma cell migration and invasion. In this study, we investigated the potential involvement of RIAM in focal adhesion (FA) dynamics. RIAM...

The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. ...

Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small ...

Platelet aggregation requires agonist-induced alphaIIbbeta3 activation, a process mediated by Rap1 and talin. To study mechanisms, we engineered alphaIIbbeta3 Chinese hamster ovary (CHO) cells to conditionally express talin and protease-activated receptor (PAR) thrombin receptors. Human PAR1 or murine PAR4 stimulation activates alphaIIbbeta3, which was measured with antibody PAC-1, indicating c...

Talin-mediated integrin activation drives integrin-based adhesions. Here we examine the roles of two proteins that induce talin-integrin interactions--vinculin and Rap1-GTP-interacting adaptor molecule (RIAM)--in the formation and maturation of integrin-based adhesions. RIAM-containing adhesions are primarily in the lamellipodium; RIAM is subsequently reduced in mature focal adhesions due to di...

The small GTPase Rap1 induces integrin activation via an inside-out signaling pathway mediated by the Rap1-interacting adaptor molecule (RIAM). Blocking this pathway may suppress tumor metastasis and other diseases that are related to hyperactive integrins. However, the molecular basis for the specific recognition of RIAM by Rap1 remains largely unknown. Herein we present the crystal structure ...

It is highly important in Japan to choose a good site for wind turbine generators, because the spatial distribution of wind speed is quite complicated over steep complex terrain. We are developing the unsteady numerical model called the RIAM-COMPACT (Research Institute for Applied Mechanics, Kyushu University, Computational Prediction of Airflow over Complex Terrain). The RIAM-COMPACT is based ...

The membrane localization and activation of cytoskeletal protein talin are key steps to initiate the integrin transmembrane receptors' activation, which mediates many cellular adhesive responses such as cell migration, spreading and proliferation. RIAM, a membrane anchor and small GTPase RAP1 effector, is known to bind to the C-terminal rod domain of talin (talin-R) and promote localizations of...

It is highly important in Japan to choose a good site for wind turbines, because the spatial distribution of wind speed is quite complicated over steep complex terrain. We are developing the unsteady numerical model called the Research Institute for Applied Mechanics, Kyushu University, COMputational Prediction of Airflow over Complex Terrain (RIAM-COMPACT). The RIAMCOMPACT is based on the larg...