Radil controls neutrophil adhesion and motility through β2-integrin activation

Liu, Lunhua; Aerbajinai, Wulin; Ahmed, Syed Mukhtar; Rodgers, Griffin P.; Angers, Stéphane; Parent, Carole A.

doi:10.1091/mbc.e12-05-0408

Cited by 23 publications

(28 citation statements)

References 63 publications

(84 reference statements)

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“…77 Platelets also express Rap2B that associates with aIIbb3 and translocates to the actin cytoskeleton on platelet stimulation. 78 Several Rap1 effectors including regulator for cell adhesion and polarization enriched in lymphoid tissues (RAPL), 79 Rap1-GTPinteracting adaptor molecule (RIAM), 80 and Ras associated and diluted domains (RADIL) 81 can link Rap1 to integrin activation or avidity in various cell types. The connection between talin and RAPL or RADIL is unknown; thus, in the section below, we focus on the mechanisms of RIAM-mediated regulation of integrin activation.…”

Section: Roles Of Rap Gtpases In Integrin-mediated Functions Of Bloodmentioning

confidence: 99%

The Rap1-RIAM-talin axis of integrin activation and blood cell function

Lagarrigue

Kim

Ginsberg

2016

Blood

127

142

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Integrin adhesion receptors mediate the adhesion of blood cells, such as leukocytes, to other cells, such as endothelial cells. Integrins also are critical for anchorage of hematopoietic precursors to the extracellular matrix. Blood cells can dynamically regulate the affinities of integrins for their ligands ("activation"), an event central to their functions. Here we review recent progress in understanding the mechanisms of integrin activation with a focus on the functions of blood cells. We discuss how talin binding to the integrin b cytoplasmic domain, in conjunction with the plasma membrane, induces long-range allosteric rearrangements that lead to integrin activation. Second, we review our understanding of how signaling events, particularly those involving Rap1 small guanosine triphosphate (GTP) hydrolases, can regulate the talin-integrin interaction and resulting activation. Third, we review recent findings that highlight the role of the Rap1-GTP-interacting adapter molecule (RIAM), encoded by the APBB1IP gene, in leukocyte integrin activation and consequently in leukocyte trafficking. (Blood. 2016;128(4):479-487) Introduction Circulating blood cells patrol the body to guard against pathogens and maintain homeostasis. The adhesive interactions of leukocytes with the blood vessel walls are transient and dynamic and serve a wide range of immune functions.1 Similarly, platelets do not stably adhere to the intact vessel wall; however, when the endothelium is disrupted, a rapid interaction between circulating platelets and the vessel leads to the formation of a platelet-leukocyte-fibrin aggregate that mediates hemostasis.2 Members of the integrin adhesion receptor family play important roles in these processes. Integrins are type 1 transmembrane receptors that mediate cell-cell and cell-extracellular matrix adhesion. 3 Each integrin heterodimer contains 1 a and 1 b subunit. In vertebrates, 18 a and 8 b subunits can form 24 integrins with characteristic tissue distributions and distinct ligand binding specificities. 3,4 Leukocyte integrins include aLb2 (LFA-1, CD11a/CD18), a4b1 (VLA-4), and aMb2 (Mac-1, CD11b/CD18), 5,6 whereas integrin aIIbb3 (GPIIbIIIa) is by far the most abundant platelet integrin. 7 Integrins sense chemical and physical properties of extracellular matrix and control signal transduction pathways that regulate cell adhesion, proliferation, differentiation, and apoptosis. 3 Mutations of integrin genes can lead to blood diseases such as leukocyte adhesion deficiency I syndrome, 8,9 due to mutations in the gene encoding integrin b2, or Glanzmann thrombasthenia, 10 due to mutations in the genes encoding aIIb or b3. Integrins in blood cells are usually in a low-affinity state until agonist stimulation induces a high-affinity form, a process operationally defined as "integrin activation." 6,[11][12][13] On platelet stimulation by agonists such as thrombin or collagen, activated aIIbb3 binds fibrinogen, fibronectin, and von Willebrand factor to enable both stable adherence to the vessel wal...

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Section: Roles Of Rap Gtpases In Integrin-mediated Functions Of Bloodmentioning

confidence: 99%

The Rap1-RIAM-talin axis of integrin activation and blood cell function

Lagarrigue

Kim

Ginsberg

2016

Blood

127

142

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“…Furthermore, expression of a Rap1-specific GAP, Spa1, completely abrogates chemokine-stimulated adhesion, polarization, and transmigration under shear flow. In neutrophil-like PLB-985 cells, expression of a constitutively active Rap1aQ63E construct causes increased cell adhesion and reduced tail retraction, leading to poor chemotaxis [227]. It should be noted that Rap2, which shares ∼60% homology with Rap1, also appears to regulate migration, although this effect might be cell-type or context-dependent [228,225,224].…”

Section: Chemotactic Network Of Dictyostelium and Leukocytesmentioning

confidence: 99%

“…Other Rap1 effectors that mediate its effects on integrin-dependent adhesion and chemotaxis include Radil, ARAP3, partitioning defective (Par) polarity complex and T lymphoma invasion and metastasis 1 (Tiam1) [227,239,226]. Treatment with fMLP triggers a rapid translocation of the adapter protein Radil to the plasma membrane of neutrophils.…”

Section: Chemotactic Network Of Dictyostelium and Leukocytesmentioning

confidence: 99%

“…Treatment with fMLP triggers a rapid translocation of the adapter protein Radil to the plasma membrane of neutrophils. Similarly to Rap1E63, overexpression of Radil leads to integrin activation, increased cell-substrate adhesion, and defects in tail retraction [227]. On the other hand, reduction of Radil by siRNA leads to reduced adhesion and chemotaxis.…”

Section: Chemotactic Network Of Dictyostelium and Leukocytesmentioning

confidence: 99%

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Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes

Artemenko

Lampert

Devreotes

2014

Cell. Mol. Life Sci.

181

221

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Chemotaxis, or directed migration of cells along a chemical gradient, is a highly coordinated process that involves gradient sensing, motility, and polarity. Most of our understanding of chemotaxis comes from studies of cells undergoing amoeboid-type migration, in particular the social amoeba Dictyostelium discoideum and leukocytes. In these amoeboid cells the molecular events leading to directed migration can be conceptually divided into four interacting networks: receptor/G protein, signal transduction, cytoskeleton, and polarity. The signal transduction network occupies a central position in this scheme as it receives direct input from the receptor/G protein network, as well as feedback from the cytoskeletal and polarity networks. Multiple overlapping modules within the signal transduction network transmit the signals to the actin cytoskeleton network leading to biased pseudopod protrusion in the direction of the gradient. The overall architecture of the networks, as well as the individual signaling modules are remarkably conserved between Dictyostelium and mammalian leukocytes, and the similarities and differences between the two systems are the subject of this review.

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“…[36] Radil has been implicated in the control of neutrophil adhesion and chemotaxis. [40] Finally, two IA associated common variants, rs12472355 and rs919433 at 2q33.1 were located 30 Kb upstream and intronic of ANKRD44, respectively. [36] ANKRD44 is a likely subunit of protein phosphotase-6 whose functions include inhibition of NF-κB activation.…”

Section: Mediators Of Inflammationmentioning

confidence: 98%

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

Dooley¹,

Hudson²,

Hasan³

2015

Neuroimmunol Neuroinflammation

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Intracranial aneurysms are a life-threatening cerebrovascular pathology with a probability of spontaneous rupture. Current intervention techniques carry inherent risk. Recent investigation has reinforced inflammation's role in the pathophysiological process of cerebral aneurysms. These data suggest alternative diagnostic and noninvasive therapeutic strategies. Furthermore, novel characteristics of the underlying disease have been elucidated through distinct bioinformatic and gene expression profile analyses. This article will emphasize the most recent investigation, highlighting findings of clinical significance and etiological relevance.

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Radil controls neutrophil adhesion and motility through β2-integrin activation

Cited by 23 publications

References 63 publications

The Rap1-RIAM-talin axis of integrin activation and blood cell function

The Rap1-RIAM-talin axis of integrin activation and blood cell function

Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

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