Genetic, biochemical and structural approaches to talin function

Critchley, David R.

doi:10.1042/bst0331308

Cited by 35 publications

(24 citation statements)

References 64 publications

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“…These results suggest that vinculin is a sensor of PIP 2 in the FA and that it promotes dynamic FA assembly and disassembly. Talin, which binds vinculin, actin, and integrin, has a key role in coupling the cytoskeleton to integrins [29]. An early study suggests that PIP 2 promotes talin/integrin interaction [87].…”

Section: Mammalian Pip5kγmentioning

confidence: 99%

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

Mao

Yin

2007

Pflugers Arch - Eur J Physiol

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Phosphatidylinositol (4,5)-bisphosphate (PIP(2)) is an important lipid mediator that has multiple regulatory functions. There is now increasing evidence that the phosphatidylinositol 4-phosphate 5 kinases (PIP5Ks), which synthesize PIP(2), are regulated spatially and temporally and that they have isoform-specific functions and regulations. This review will summarize the highlights of recent developments in understanding how the three major PIP5K isoforms regulate the actin cytoskeleton and other important cellular processes.

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Section: Mammalian Pip5kγmentioning

confidence: 99%

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

Mao

Yin

2007

Pflugers Arch - Eur J Physiol

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“…The knockdown of Talin1 results in an intracellular uncoupling of the linkage between all known integrins and the actin cytoskeleton. 35 Accordingly, increased retrograde actin flow in both CD81 Ϫ/Ϫ and Talin1 RNAi knockdown BM-DCs provoked increased actin polymerization rates, because membrane protrusion speed was unaltered (supplemental Figure 3). Similar findings were described before for integrin-deficient DCs.…”

Section: Cd81 Regulates Integrin-dependent Adhesion and Retrograde Acmentioning

confidence: 99%

CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration

Quast

Eppler

Semmling

et al. 2011

Blood

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CD81 (TAPA-1) is a member of the widely expressed and evolutionary conserved tetraspanin family that forms complexes with a variety of other cell surface receptors and facilitates hepatitis C virus entry. Here, we show that CD81 is specifically required for the formation of lamellipodia in migrating dendritic cells (DCs). Mouse CD81 ؊/؊ DCs, or murine and human CD81 RNA interference knockdown DCs lacked the ability to form actin protrusions, thereby impairing their motility dramatically. Moreover, we observed a selective loss of Rac1 activity in the absence of CD81, the latter of which is exclusively required for integrin-dependent migration on 2-dimensional substrates. Neither integrin affinity for substrate nor the size of basal integrin clusters was affected by CD81 deficiency in adherent DCs. However, the use of total internal reflection fluorescence microscopy revealed an accumulation of integrin clusters above the basal layer in CD81 knockdown cells. Furthermore, ␤1-or ␤2-integrins, actin, and Rac are strongly colocalized at the leading edge of DCs, but the very fronts of these cells protrude CD81-containing membranes that project outward from the actin-integrin area. Taken together, these data suggest a thus far unappreciated role for CD81 in the mobilization of preformed integrin clusters into the leading edge of migratory DCs on 2-dimensional

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“…RAW 264.7 (ATCC no. TIB-7) and talin conditional knockout mouse embryo fibroblasts (Critchley, 2005) were maintained in DMEM (Invitrogen) supplemented with 10% heat-inactivated fetal bovine serum (PAA Laboratories, Coelbe, Germany). COS-7 cells were transfected using the DEAE-dextran method (Caron and Hall, 1998), talin conditional knockout cells were transfected using SuperFect (QIAGEN).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…The talin molecule is composed of two main regions: the N-terminal head region (ca. 50 kDa) contains a FERM (band 4.1, ezrin, radixin, moesin) domain, which binds to the cytoplasmic domain of ␤-integrin subunits and layilin, a C-type lectin, whereas the large rod domain harbors F-actin-and vinculin-binding sites (Critchley, 2005). Studies in a variety of cell systems and organisms suggest that talin can play distinct cellular roles in different contexts.…”

Section: Introductionmentioning

confidence: 99%

An Essential Role for Talin during α_Mβ₂-mediated Phagocytosis

Lim

Wiedemann

Tzircotis

et al. 2007

MBoC

102

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The cytoskeletal, actin-binding protein talin has been previously implicated in phagocytosis in Dictyostelium discoideum and mammalian phagocytes. However, its mechanism of action during internalization is not understood. Our data confirm that endogenous talin can occasionally be found at phagosomes forming around IgG-and C3bi-opsonized red blood cells in macrophages. Remarkably, talin knockdown specifically abrogates uptake through complement receptor 3 (CR3, CD11b/CD18, ␣ M ␤ 2 integrin) and not through the Fc ␥ receptor. We show that talin physically interacts with CR3/␣ M ␤ 2 and that this interaction involves the talin head domain and residues W747 and F754 in the ␤ 2 integrin cytoplasmic domain. The CR3/␣ M ␤ 2 -talin head interaction controls not only talin recruitment to forming phagosomes but also CR3/␣ M ␤ 2 binding activity, both in macrophages and transfected fibroblasts. However, the talin head domain alone cannot support phagocytosis. Our results establish for the first time at least two distinct roles for talin during CR3/␣ M ␤ 2 -mediated phagocytosis, most noticeably activation of the CR3/␣ M ␤ 2 receptor and phagocytic uptake. INTRODUCTIONPhagocytosis is an essential physiological function, common to most eukaryotic cell types. From serving a feeding role in amoebae, phagocytosis is observed in Metazoa as a homeostatic process that ensures the removal of microorganisms and apoptotic cells (Desjardins et al., 2005). Classically, phagocytosis is a multistep process that sequentially involves receptor-mediated particle recognition, actin-driven uptake, phagosome maturation and particle clearance. Numerous phagocytic receptors exist that can bind their target directly or indirectly through opsonins (Underhill and Ozinsky, 2002). Receptors for phagocytosis can show constitutive or inducible binding activities, as illustrated for the two bestcharacterized phagocytic receptors: the Fc ␥ receptor (Fc␥R) for complexed IgG and complement receptor 3 (CR3, CD11b/ CD18, ␣ M ␤ 2 integrin), respectively (Bianco et al., 1975). Ligand-bound receptors classically zipper around the phagocytic prey and induce intracellular signaling cascades that lead to the activation and recruitment of signaling and adaptor molecules at sites of particle binding. These locally assembled signaling complexes reorganize the actin cytoskeleton and regulate membrane dynamics underneath bound particles through the activation of Rho-and Arf-family GTPbinding proteins, respectively (Cougoule et al., 2004). According to the zipper model, phagocytosis of bound particles requires continual ligation of phagocytic receptors around the whole phagocytic object, at least for spherical particles Champion and Mitragotri, 2006). Several cytoskeletal proteins have been shown to be recruited to phagocytic cups, although their role is not always defined. Talin, a cytoskeletal protein of 2541 amino acids and 270 kDa has been repeatedly implicated in phagocytosis. Immunofluorescence studies of phagocytozing macrophages have shown that talin accumulates...

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Genetic, biochemical and structural approaches to talin function

Cited by 35 publications

References 64 publications

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration

An Essential Role for Talin during α_Mβ₂-mediated Phagocytosis

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Genetic, biochemical and structural approaches to talin function

Cited by 35 publications

References 64 publications

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration

An Essential Role for Talin during αMβ2-mediated Phagocytosis

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An Essential Role for Talin during α_Mβ₂-mediated Phagocytosis