Affinage

Showing APBB1IP — RIAM is a alias.

APBB1IP

Amyloid beta A4 precursor protein-binding family B member 1-interacting protein · UniProt Q7Z5R6

Length
666 aa
Mass
73.2 kDa
Annotated
2026-06-09
33 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APBB1IP (RIAM) is a multidomain Rap1-effector scaffold that couples small-GTPase signaling to integrin activation and actin-based motility (PMID:15469846, PMID:19098287). It was first identified as a Rap1-GTP-interacting adaptor that also binds Profilin and Ena/VASP proteins, and whose activity is required to retain Rap1-GTP at the plasma membrane and drive integrin activation, cell spreading, and lamellipodia formation (PMID:15469846). The core of its function is a relay that recruits talin to the membrane: RIAM binds active Rap1 through its RA-PH module — with a Rap1 Lys31–RIAM Glu212 salt bridge serving as the specificity determinant (PMID:24287201) — and binds talin directly via short N-terminal amphipathic helices, such that a minimized Rap-RIAM module is sufficient to recruit talin and activate integrins (PMID:19098287, PMID:22523535). RIAM additionally engages the talin head to sterically displace the talin rod domain that masks the integrin-binding site, conformationally unmasking talin to promote inside-out integrin activation (PMID:25520155). RIAM activity is gated by autoinhibition: an intramolecular IN–RA-PH interaction suppresses Rap1 binding and is released by FAK-dependent phosphorylation of Tyr45, while Src-mediated phosphorylation of PH-domain residues Tyr267/Tyr427 unmasks the PIP2-binding site to enable membrane recruitment (PMID:30733287, PMID:33275877). At the cell periphery RIAM forms a trimeric MRL–integrin–talin complex at the tips of lamellipodial and filopodial protrusions (PMID:26419705) and engages vinculin within the focal-adhesion talin-vinculin complex in a force-independent manner (PMID:41454178); it also controls focal-adhesion disassembly through a RhoA–MEK–Erk pathway (PMID:22946047). In vivo, RIAM is essential in leukocytes for β2 integrin activation, adhesion to inflamed vessels, and trafficking to lymphoid organs, while being dispensable for platelet integrins (PMID:26337492, PMID:26324702), and it is required for immunological synapse formation and complement-mediated (CR3/αMβ2) phagocytosis (PMID:28348273, PMID:23420480).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2004 High

    Established RIAM as the molecular link between active Rap1 and integrin activation, answering how Rap1-GTP signals are converted into adhesion and actin remodeling.

    Evidence Yeast two-hybrid, reciprocal co-IP/pulldown, and RNAi with adhesion, spreading, and integrin-activation readouts

    PMID:15469846

    Open questions at the time
    • Did not resolve the structural basis of Rap1 recognition
    • Mechanism connecting RIAM to integrins (via talin) not yet defined
  2. 2006 Medium

    Showed an evolutionarily conserved role for the RIAM ortholog MIG-10 in actin-based guidance, linking it genetically to Ena/VASP downstream of netrin and slit cues.

    Evidence Genetic epistasis and overexpression phenotypes in C. elegans plus actin colocalization in cultured cells

    PMID:16563765

    Open questions at the time
    • Ortholog-based; mammalian RIAM guidance role not directly tested
    • Biochemical nature of MIG-10/UNC-34 interaction not defined
  3. 2007 Medium

    Connected RIAM to TCR signaling by identifying the ADAP/SKAP-55 module as the means by which RIAM and Rap1 are relocalized to the membrane for integrin activation in T cells.

    Evidence Reciprocal co-IP in primary T cells, domain mapping, RNAi with adhesion/conjugate assays

    PMID:17403904

    Open questions at the time
    • Single lab
    • Stoichiometry and direct-versus-indirect nature of the RIAM–SKAP-55 interface not resolved
  4. 2008 High

    Defined the membrane-recruitment mechanism, showing RIAM bridges Rap1 membrane targeting to talin via N-terminal amphipathic helices and that a minimal Rap-RIAM chimera suffices to activate integrins.

    Evidence In vitro binding, amphipathic-helix mutagenesis, chimeric Rap-RIAM module, integrin-activation assays

    PMID:19098287

    Open questions at the time
    • Did not address how talin is conformationally activated
    • Regulation of RIAM autoinhibition not yet known
  5. 2009 Medium

    Extended RIAM beyond integrins by showing it positions PLC-γ1 at the actin cytoskeleton near PIP2 to enable downstream TCR signaling (calcium, NFAT, IL-2).

    Evidence shRNA knockdown plus rescue, calcium flux, inositol phosphate, NFAT imaging, co-IP

    PMID:19952372

    Open questions at the time
    • Direct RIAM–PLC-γ1 binding interface not mapped
    • Single lab
  6. 2010 Medium

    Revealed RIAM as a node integrating integrin crosstalk, where dephosphorylated VASP preferentially forms a RIAM–VASP complex that promotes talin–β1 integrin activation.

    Evidence In vitro binding, β3-null fibroblasts, co-IP, focal adhesion imaging, migration assays

    PMID:20404115

    Open questions at the time
    • Quantitative contribution of RIAM–VASP versus RIAM–talin axes not separated
    • Single lab
  7. 2011 Medium

    Implicated RIAM in tumor cell invasion through a Vav2–RhoA–ROCK–myosin pathway controlling migration directionality.

    Evidence siRNA with constitutively active Vav2/RhoA rescue, xenografts, invasion and kinase assays

    PMID:21454517

    Open questions at the time
    • Mechanism linking RIAM to Vav2/RhoA activation undefined
    • Single lab/cell-type
  8. 2012 Medium

    Showed RIAM is required for focal-adhesion turnover, defining a RIAM→RhoA→MEK→Erk pathway that drives FA disassembly and invasion.

    Evidence siRNA, live-cell FA imaging, constitutively active MEK/RhoA rescue, FA-protein co-IP

    PMID:22946047

    Open questions at the time
    • Reconciling RIAM's pro-assembly (integrin activation) and pro-disassembly roles unresolved
    • Single lab
  9. 2012 Medium

    Dissected the Rap1-binding module, establishing the RA domain as sufficient for GTP-dependent Rap1B binding and the PH domain as a stabilizer, plus a GTP-independent N-terminal contact.

    Evidence In vitro binding, domain truncation, stability assays

    PMID:22523535

    Open questions at the time
    • Functional role of the GTP-independent contact unclear
    • Single study
  10. 2013 High

    Provided the atomic basis of Rap1 recognition, identifying the Rap1 Lys31–RIAM Glu212 salt bridge as the specificity determinant.

    Evidence 1.65 Å crystal structure of Rap1–RA-PH, mutagenesis, co-IP, adhesion assays

    PMID:24287201

    Open questions at the time
    • Structure of the full-length autoinhibited protein not captured
    • Membrane-engagement geometry not addressed
  11. 2013 Medium

    Defined a selective physiological role: RIAM is required for complement-receptor (αMβ2)-mediated phagocytosis but not IgG-mediated phagocytosis, acting by recruiting talin to the β2 tail.

    Evidence siRNA in myeloid lines and primary macrophages, phagocytosis assays, talin–β2 co-IP

    PMID:23420480

    Open questions at the time
    • Single lab
    • Outside-in signaling component not yet defined
  12. 2014 High

    Uncovered RIAM's talin-conformational role: binding the talin head sterically displaces the masking talin rod domain to unmask the integrin-binding site.

    Evidence Systematic pulldown/co-IP binding mapping, mutagenesis, integrin-activation assays

    PMID:25520155

    Open questions at the time
    • Structure of the RIAM-talin-head complex not solved
    • Kinetics of unmasking in cells not quantified
  13. 2015 High

    Visualized the trimeric MRL–integrin–talin complex at protrusion tips, showing talin bridges RIAM to integrins and that this complex is needed for cell protrusion.

    Evidence Live-cell BiFC, dominant-negative disruption, protrusion assays

    PMID:26419705

    Open questions at the time
    • Spatial relationship to actin-polymerization machinery at tips not resolved
  14. 2015 High

    Established the in vivo leukocyte requirement: RIAM-null mice fail to activate β2 integrins and show impaired vascular adhesion and lymphocyte trafficking, while platelet integrins are spared.

    Evidence RIAM knockout mice, flow cytometry, intravital microscopy, bone marrow transplant, antibody responses

    PMID:26324702 PMID:26337492

    Open questions at the time
    • Molecular basis for the platelet-versus-leukocyte selectivity not fully explained
  15. 2017 Medium

    Linked RIAM to adaptive immunity, showing it is recruited with talin and LFA-1 to immunological synapses and is required for conjugate formation, proliferation, and cytotoxicity.

    Evidence RIAM-null T cells, synapse imaging, conjugate and cytotoxicity assays, adoptive transfer

    PMID:28348273

    Open questions at the time
    • Single lab
    • Direct synapse-recruitment cue not isolated
  16. 2017 Medium

    Defined the talin R3 domain as a mechanosensitive switch that thermodynamically selects between RIAM (closed) and vinculin (open), explaining force-dependent handover at adhesions.

    Evidence NMR pressure perturbation, thermodynamic modeling, R3 mutagenesis

    PMID:29153504

    Open questions at the time
    • Finding centers on talin conformation, not direct RIAM mechanism
    • Single lab
  17. 2019 High

    Explained how RIAM is switched on, with a crystal structure showing an autoinhibitory IN–RA-PH interaction released by FAK-dependent Tyr45 phosphorylation to permit Rap1 binding and membrane translocation.

    Evidence 2.4 Å crystal structure, Tyr45 mutagenesis, FAK inhibitors, adhesion and translocation assays

    PMID:30733287

    Open questions at the time
    • Upstream signals activating FAK toward Tyr45 not mapped
    • Phosphatase reversing the switch unknown
  18. 2020 High

    Identified a second activating switch: Src phosphorylation of PH-domain Tyr267/Tyr427 disrupts an interface masking the PIP2-binding site, enabling membrane recruitment.

    Evidence Structural analysis, Tyr267/Tyr427 mutagenesis, Src kinase and integrin-activation assays

    PMID:33275877

    Open questions at the time
    • Coordination between FAK-Tyr45 and Src-PH switches not defined
  19. 2020 Medium

    Extended RIAM into outside-in signaling, showing the RIAM–VASP complex relays complement-receptor signals to drive VASP recruitment, pSer157-VASP, and actin-rich phagocytic cup formation.

    Evidence CRISPR knockout of RIAM and VASP in HL-60, VASP-EGFP live imaging, phagocytosis and phospho-flow assays

    PMID:32397169

    Open questions at the time
    • Single lab
    • Direct link from integrin engagement to VASP phosphorylation not fully traced
  20. 2021 Medium

    Used compound mutant mice to establish that Rap1-direct and RIAM-mediated talin pathways are the two primary β2 integrin regulatory mechanisms in leukocytes.

    Evidence Rap1-binding talin1 mutant × RIAM-KO mice, intravital microscopy, Hoxb8 neutrophils, β2 conformation flow cytometry

    PMID:34489950

    Open questions at the time
    • Quantitative apportioning of the two pathways across leukocyte subsets incomplete
  21. 2021 Medium

    Revealed a transcriptional role: RIAM controls αMβ2/αXβ2 integrin mRNA expression during neutrophilic differentiation via an actin–MRTF-A–SRF pathway.

    Evidence CRISPR KO in HL-60, RT-qPCR, jasplakinolide rescue, MRTF-A localization, VASP knock-in rescue

    PMID:36238292

    Open questions at the time
    • Direct demonstration of SRF occupancy at ITGAM/ITGAX promoters absent
    • Single lab
  22. 2025 Medium

    Demonstrated that RIAM binds the vinculin N-terminus within the focal-adhesion talin-vinculin complex in a force-independent manner, refining the adhesion interaction network.

    Evidence Three-color FRET-cascade TCSPC-FLIM in live cells, purified-protein validation, negative-staining TEM, tension sensors

    PMID:41454178

    Open questions at the time
    • Structural interface of RIAM–vinculin contact not solved
    • Single lab/single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the FAK-Tyr45 and Src-PH activation switches are temporally and spatially coordinated with Rap1 loading, and how RIAM's pro-adhesion roles are reconciled with its pro-FA-disassembly and transcriptional functions, remains unresolved.
  • No integrated model coupling the two phospho-switches in vivo
  • Phosphatases/timing controlling switch reversal unknown
  • Mechanistic basis for context-dependent assembly versus disassembly roles unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1474244 Extracellular matrix organization 4
Partners
ITGB2PFN1PLCG1RAP1ASKAP-55TLN1VASPVCL
Complex memberships
ADAP/SKAP-55 signaling moduleMRL protein-integrin-talin (MIT) complextalin-vinculin-RIAM focal adhesion complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RIAM was identified as a Rap1-GTP-interacting adaptor molecule that directly interacts with active Rap1 (GTP-bound), Profilin, and Ena/VASP proteins. RIAM overexpression induced cell spreading, lamellipodia formation, integrin activation, and cell adhesion; knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion and reduced polymerized actin content. Yeast two-hybrid, co-immunoprecipitation, pulldown assays, RNAi knockdown with cell adhesion and spreading assays, flow cytometry for integrin activation Developmental cell High 15469846
2008 RIAM functions as a scaffold connecting membrane-targeting sequences of Ras GTPases (Rap1) to talin, thereby recruiting talin to the plasma membrane to activate integrins. RIAM binds directly to talin via short N-terminal amphipathic helix sequences, and a minimized 50-residue Rap-RIAM module (talin-binding site of RIAM joined to the membrane-targeting sequence of Rap1A) is sufficient to recruit talin and activate integrins. In vitro binding assays, mutagenesis of amphipathic helix sequences, cell-based integrin activation assays, construction of chimeric Rap-RIAM module The Journal of biological chemistry High 19098287
2006 MIG-10 (the C. elegans RIAM ortholog) functions downstream of the attractive guidance cue UNC-6/netrin and repulsive cue SLT-1/slit to direct axon migration. MIG-10 interacts with UNC-34 (Ena/VASP ortholog) to mediate responses to guidance cues, and colocalizes with actin in cultured cells where it can induce lamellipodia formation. Genetic epistasis analysis in C. elegans, overexpression phenotype analysis, co-localization with actin in cultured cells Current biology : CB Medium 16563765
2007 RIAM constitutively interacts with SKAP-55 (component of the ADAP/SKAP-55 signaling module) in both heterologous transfection systems and primary T cells, linking the ADAP/SKAP-55 module to Rap1 for TCR-mediated integrin activation. Following TCR activation, the ADAP/SKAP-55 module relocalized RIAM and Rap1 to the plasma membrane. Co-immunoprecipitation in primary T cells and transfection systems, domain mapping, RNAi knockdown with T cell adhesion and conjugate formation assays Molecular and cellular biology Medium 17403904
2009 RIAM is required for TCR-mediated PLC-γ1 translocation to the actin cytoskeleton in T cells. RIAM knockdown impaired inositol trisphosphate generation, intracellular calcium mobilization, NFAT nuclear translocation, Ras-GRP1 activation, and IL-2 gene expression, while ZAP-70 phosphorylation and LAT signalosomes were unaffected. RIAM positions PLC-γ1 near its substrate PIP2. shRNA knockdown, rescue with RIAM reconstitution, calcium flux assays, inositol phosphate measurement, nuclear NFAT localization by imaging, co-immunoprecipitation Science signaling Medium 19952372
2010 Loss of β3 integrin leads to dephosphorylation of VASP (via loss of PKA-dependent phosphorylation), and dephosphorylated VASP preferentially associates with RIAM both in vitro and in vivo, forming an enhanced VASP-RIAM complex at focal adhesions that promotes talin binding to β1 integrin, revealing a mechanism by which αvβ3 locally suppresses β1 integrin activation. In vitro binding assays (VASP-RIAM interaction), β3-null fibroblasts, co-immunoprecipitation, focal adhesion immunofluorescence, migration assays The Journal of cell biology Medium 20404115
2011 RIAM is required for BLM melanoma cell invasion and tumor growth. RIAM silencing impairs persistent cell migration directionality via deficient activation of a Vav2-RhoA-ROCK-myosin light chain pathway. Constitutively active Vav2 and RhoA partially rescued invasion in RIAM-depleted cells. RIAM depletion also reduces β1 integrin-dependent adhesion and decreases Erk1/2 MAPK and PI3K activation. siRNA knockdown, rescue with constitutively active Vav2 and RhoA, xenograft mouse model, cell invasion assays, integrin activation assays, kinase activation assays The Journal of biological chemistry Medium 21454517
2012 RIAM is required for focal adhesion (FA) disassembly: RIAM depletion in melanoma and breast carcinoma cells causes increased FA number, size, and stability due to defective FA disassembly. This is mediated through a RIAM→RhoA→MEK→Erk1/2 pathway downstream of integrin engagement; constitutively active MEK rescued FA disassembly and cell invasion in RIAM-depleted cells. RIAM depletion also weakened associations between FA proteins. siRNA knockdown, live cell imaging of FA dynamics, rescue with constitutively active MEK and RhoA, kinase activation assays, co-immunoprecipitation of FA proteins Journal of cell science Medium 22946047
2012 The RA domain of RIAM is sufficient for GTP-dependent interaction with Rap1B; addition of the PH domain does not change binding affinity but stabilizes the RA domain both in vitro and in cells. A GTP-independent interaction between Rap1B and the N-terminus of RIAM was also detected. In vitro binding assays, domain truncation analysis, stability assays PloS one Medium 22523535
2013 Crystal structure of GTP-bound Rap1 in complex with the RA-PH module of RIAM at 1.65 Å resolution reveals that Rap1 Lys31 forms a salt bridge with RIAM Glu212 as the key specificity determinant. Disruption of these interactions reduces Rap1:RIAM association, co-clustering, and cell adhesion. X-ray crystallography at 1.65 Å, site-directed mutagenesis, co-immunoprecipitation, cell adhesion assays Journal of molecular cell biology High 24287201
2013 RIAM is required for complement-mediated (CR3/αMβ2-dependent) phagocytosis but not IgG-mediated phagocytosis in myeloid cells. RIAM knockdown impairs αMβ2 integrin affinity changes and blocks Rap1-induced complement phagocytosis enhancement. RIAM mediates its function by recruiting talin to the β2 integrin cytoplasmic tail during phagocytosis. siRNA knockdown in HL-60 and THP-1 cell lines and primary macrophages, phagocytosis assays with complement- and IgG-opsonized particles, co-immunoprecipitation of talin with β2 integrin, EPAC-mediated Rap1 activation Cellular and molecular life sciences : CMLS Medium 23420480
2014 RIAM binds not only to the talin rod (talin-R) but also to the talin head (talin-H). RIAM binding to talin-H sterically occludes a talin-R domain that otherwise masks the integrin-binding site on talin-H, thereby conformationally unmasking talin and promoting integrin activation. This reveals a novel role for RIAM in talin conformational regulation. Systematic binding mapping by pulldown and co-immunoprecipitation, mutagenesis, functional integrin activation assays Nature communications High 25520155
2015 RIAM (MRL protein) forms a complex with talin and activated integrins at the tips of growing actin filaments in lamellipodial and filopodial protrusions ('sticky fingers'). Talin bridges MRL proteins to integrins to form this MRL protein-integrin-talin (MIT) complex. Disruption of the MIT complex markedly impairs cell protrusion. Bimolecular fluorescence complementation (BiFC) in live cells, dominant-negative disruption of MIT complex, cell protrusion assays Nature communications High 26419705
2015 RIAM deficiency in mice results in loss of β2 integrin activation in multiple leukocyte populations, impaired leukocyte adhesion to inflamed vessels, and accumulation in circulation, demonstrating leukocyte-specific requirement for RIAM. By contrast, β1 integrin family member α4β1 was only partially affected, and platelet integrin activation was unaffected. RIAM knockout mice, β2 integrin activation assays by flow cytometry, intravital microscopy of leukocyte adhesion, bone marrow transplantation Blood High 26337492
2015 RIAM-deficient mice show defective lymphocyte adhesion to ICAM-1 and VCAM-1 and impaired trafficking of lymphocytes to secondary lymphoid organs (peripheral lymph nodes and bone marrow), associated with defective humoral immunity to T-cell-dependent antigens. Platelet function was intact in RIAM-deficient animals. RIAM knockout mice, conditional Rap1a/Rap1b double knockout, lymphocyte adhesion assays, flow cytometric trafficking analysis, antibody responses Blood High 26324702
2017 The talin R3 domain (which contains a RIAM binding site) is thermodynamically poised to bind either RIAM (closed conformation) or vinculin (open conformation), functioning as a mechanosensitive conformational switch. A mutant of R3 that retains RIAM binding but binds vinculin more weakly is 0.84 kJ/mol more stable when closed. NMR pressure perturbation with 1H, 15N, 13C chemical shift analysis, thermodynamic modeling, mutagenesis of R3 domain Structure (London, England : 1993) Medium 29153504
2017 RIAM expression in T cells is required for formation of immunological synapses: RIAM is recruited to immune synapses along with talin and LFA-1, and loss of RIAM profoundly suppresses antigen-dependent conjugate formation between T cells and APCs, Ag-driven proliferation, and cytotoxic killing. Adoptive transfer diabetes model, RIAM-null T cells, immunological synapse imaging, T cell-APC conjugate formation assays, cytotoxicity assays Journal of immunology (Baltimore, Md. : 1950) Medium 28348273
2019 RIAM is autoinhibited by an intramolecular interaction between its N-terminal IN region (aa 27–93) and the RA-PH module, which suppresses Rap1 association. Crystal structure of the IN-RA-PH module at 2.4 Å reveals the structural basis. Phosphorylation of Tyr45 in the IN segment releases autoinhibition; FAK inhibitors block Tyr45 phosphorylation, inhibit RIAM translocation to the plasma membrane, and inhibit integrin-mediated cell adhesion in a Tyr45-dependent manner. X-ray crystallography at 2.4 Å, site-directed mutagenesis at Tyr45, FAK-specific inhibitors, cell adhesion assays, RIAM plasma membrane translocation assays Proceedings of the National Academy of Sciences of the United States of America High 30733287
2020 RIAM-VASP complex functions as a relay for integrin complement receptors in outside-in signaling during complement-dependent phagocytosis. RIAM deficiency impaired particle internalization and downstream integrin signaling. RIAM is required for recruitment of VASP to phagocytic cups, VASP phosphorylation (pSer157-VASP), and formation of actin-rich phagocytic cups. CRISPR-Cas9 knockout of RIAM and VASP in HL-60 cells, VASP-EGFP overexpression with live imaging at phagocytic cups, phagocytosis assays, phospho-VASP flow cytometry Cells Medium 32397169
2020 Src family kinases phosphorylate RIAM at Tyr267 and Tyr427 in the PH domain, disrupting an intermolecular PH-mediated interface that normally masks the PIP2-binding site. This unmasks the membrane PIP2-binding site and promotes integrin activation and RIAM recruitment to the plasma membrane. Structural analysis, site-directed mutagenesis at Tyr267 and Tyr427, Src kinase assays, integrin activation assays, plasma membrane localization assays Structure (London, England : 1993) High 33275877
2021 Binding of both Rap1 and RIAM to talin1 synergistically regulates β2 integrin conformation and leukocyte trafficking. Using Rap1-binding mutant talin1 mice crossed with RIAM-deficient mice, simultaneous loss of both pathways produces a rolling phenotype similar to complete talin1 deficiency, indicating that Rap1-direct and RIAM-mediated pathways to talin are the primary β2 integrin regulatory mechanisms in leukocytes. Compound mutant mice (Rap1-binding talin1 mutant × RIAM knockout), intravital microscopy, Hoxb8 cell-derived neutrophils, flow cytometric β2 integrin conformation assays, adoptive transfer experiments Frontiers in immunology Medium 34489950
2021 RIAM controls expression of the phagocytic integrin receptors αMβ2 and αXβ2 at the mRNA level during neutrophilic differentiation. RIAM (as well as VASP and Vinculin) KO cells showed reduced F-actin content that correlated with reduced ITGAM and ITGAX mRNA. The SRF coactivator MRTF-A (which requires actin polymerization) showed cytoplasmic mislocalization in RIAM KO cells, suggesting RIAM regulates integrin gene expression via an actin-MRTF-A-SRF transcriptional pathway. CRISPR-Cas9 knockout in HL-60 cells, RT-qPCR for integrin mRNAs, jasplakinolide actin stabilization rescue, MRTF-A and FHL-2 immunofluorescence localization, VASP knock-in rescue Frontiers in immunology Medium 36238292
2025 RIAM binds to the N-terminus of vinculin in focal adhesions in a force-independent manner, as demonstrated by a three-color FRET-cascade TCSPC-FLIM system validated with purified proteins and negative-staining TEM. The RIAM-vinculin interaction occurs within the talin-vinculin-RIAM multiprotein complex at focal adhesions. Three-fluorophore FRET-cascade with TCSPC-FLIM in live vinculin KO fibroblasts reconstituted with constructs, purified protein validation, negative-staining TEM, vinculin tension sensors Communications chemistry Medium 41454178

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Developmental cell 334 15469846
2008 RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. The Journal of biological chemistry 239 19098287
2016 The Rap1-RIAM-talin axis of integrin activation and blood cell function. Blood 112 27207789
2007 RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activation. Molecular and cellular biology 96 17403904
2015 A RIAM/lamellipodin-talin-integrin complex forms the tip of sticky fingers that guide cell migration. Nature communications 68 26419705
2010 Alpha v beta3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration. The Journal of cell biology 67 20404115
2015 Loss of the Rap1 effector RIAM results in leukocyte adhesion deficiency due to impaired β2 integrin function in mice. Blood 66 26337492
2014 Conformational activation of talin by RIAM triggers integrin-mediated cell adhesion. Nature communications 65 25520155
2015 Rap1 and its effector RIAM are required for lymphocyte trafficking. Blood 62 26324702
2006 UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin. Current biology : CB 60 16563765
2011 Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells. The Journal of biological chemistry 35 21454517
2012 Focal adhesion disassembly is regulated by a RIAM to MEK-1 pathway. Journal of cell science 28 22946047
2019 Molecular basis for autoinhibition of RIAM regulated by FAK in integrin activation. Proceedings of the National Academy of Sciences of the United States of America 26 30733287
2009 RIAM regulates the cytoskeletal distribution and activation of PLC-gamma1 in T cells. Science signaling 24 19952372
2013 RIAM (Rap1-interacting adaptor molecule) regulates complement-dependent phagocytosis. Cellular and molecular life sciences : CMLS 23 23420480
2017 The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression. Science signaling 22 28831022
2013 The structure of Rap1 in complex with RIAM reveals specificity determinants and recruitment mechanism. Journal of molecular cell biology 21 24287201
2006 Rap1 regulation of RIAM and cell adhesion. Methods in enzymology 20 16757337
2020 RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment. Cells 15 32397169
2020 Phosphorylation of RIAM by src promotes integrin activation by unmasking the PH domain of RIAM. Structure (London, England : 1993) 15 33275877
2017 Pressure-Dependent Chemical Shifts in the R3 Domain of Talin Show that It Is Thermodynamically Poised for Binding to Either Vinculin or RIAM. Structure (London, England : 1993) 15 29153504
2021 Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking. Frontiers in immunology 14 34489950
2017 Cutting Edge: Loss of T Cell RIAM Precludes Conjugate Formation with APC and Prevents Immune-Mediated Diabetes. Journal of immunology (Baltimore, Md. : 1950) 12 28348273
2021 Structural, biochemical, and functional properties of the Rap1-Interacting Adaptor Molecule (RIAM). Biomedical journal 10 34601137
2019 A Cross-Species Systems Genetics Analysis Links APBB1IP as a Candidate for Schizophrenia and Prepulse Inhibition. Frontiers in behavioral neuroscience 10 31920576
2015 The Rap1-RIAM pathway prefers β2 integrins. Blood 8 26679542
2022 RIAM: A Universal Accessible Protocol for the Isolation of High Purity DNA from Various Soils and Other Humic Substances. Methods and protocols 7 36548141
2022 Expression of the phagocytic receptors αMβ2 and αXβ2 is controlled by RIAM, VASP and Vinculin in neutrophil-differentiated HL-60 cells. Frontiers in immunology 6 36238292
2012 Binding properties and stability of the Ras-association domain of Rap1-GTP interacting adapter molecule (RIAM). PloS one 6 22523535
2021 TLR4 inhibition ameliorated glucolipotoxicity-induced differentiation suppression in osteoblasts via RIAM regulation of NF-κB nuclear translocation. Molecular and cellular endocrinology 5 34929310
2021 Phosphorylation of RIAM Activates Its Adaptor Function in Mediating Integrin Signaling. Journal of cellular signaling 2 35128538
2025 Application of the modified RIAM method in assessing the environmental impact of municipal solid waste management scenarios (A case study). Heliyon 0 39882464
2025 Development of three-colour FRET cascade for force sensing of the putative RIAM-vinculin interaction in fibroblasts. Communications chemistry 0 41454178

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