ReviewCell Biology

The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression

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Science Signaling  22 Aug 2017:
Vol. 10, Issue 493, eaam8298
DOI: 10.1126/scisignal.aam8298

Figures

  • Fig. 1 Structure of RIAM and its homologs.

    (A) Schematic representation of the domain structure of human RIAM with other MRL family proteins. The proline-rich (PR), RA, and PH domains are noted. Asterisks indicate coiled-coil regions. (B) Human RIAM is proline-rich and contains six putative profilin-binding motifs (gray shading) and six EVH1-binding motifs (underlined).

  • Fig. 2 RIAM domains and their molecular interactions.

    The domains of RIAM mediate multiple distinct interactions, thus involving RIAM in multiple cellular functions.

  • Fig. 3 RIAM is an important component of the integrin activation machinery.

    (A) Domain organization of talin. The N-terminal talin-H is composed of F0, F1, F2, and F3 subdomains. The C-terminal talin-R is composed of 13 helical bundles (R1 to R13) followed by a dimerization domain (DD). (B) Model for talin membrane recruitment and activation. Upon agonist-mediated stimulation, talin is recruited to the plasma membrane by binding to membrane PI(4,5)P2 and the Rap1-RIAM complex. These interactions promote a conformational change in talin mediated by two distinct and synergistic mechanisms that cooperatively unmask the integrin-binding site at the F3 subdomain of the talin head. (C) The N-terminal portion of RIAM (and possibly other MRL proteins) binds to and recruits talin to the integrin cytoplasmic tail to induce integrin activation. The C-terminal portion of RIAM and other MRL proteins stimulate processive actin polymerization, in part, by recruiting Ena/VASP, thereby propelling the movement of the “sticky fingers” ends of lamellipodia and filopodia.

  • Fig. 4 RIAM in innate immune responses.

    (A) RIAM enhances pathogen clearance through complement-mediated phagocytosis and ROS production. (B) RIAM is required for neutrophil migration, adhesion, extravasation, and polarity in response to chemokines. (C) RIAM is involved in activation of integrin αMβ2 (Mac-1), which is a critical step in the cooperative actions of neutrophils and platelets in producing neutrophil extracellular traps (NETs). (D) RIAM is involved in talin recruitment to the integrin cytoplasmic tail and Pyk2 activation, which are critical events for NK cell cytotoxic function.

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