Control of High Affinity Interactions in the Talin C Terminus

Himmel, Mirko; Ritter, Anett; Rothemund, Sven; Pauling, Björg V.; Rottner, Klemens; Gingras, Alexandre R.; Ziegler, Wolfgang

doi:10.1074/jbc.m900266200

Cited by 39 publications

(41 citation statements)

References 45 publications

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“…Testes, kidney and brain express short C‐terminal proteins lacking the FERM domain 36 raising the possibility that such variants might function independent of integrins, although they do contain the integrin‐binding site located in the rod domain. Intriguingly, expression of a C‐terminal talin1 fragment resembling the testes‐specific talin2 isoform was sufficient to rescue cell cycle progression in talin1‐depleted cells suggesting a role in cellular signalling 37, 38.…”

Section: Structure Of Talin 1 Andmentioning

confidence: 98%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

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Section: Structure Of Talin 1 Andmentioning

confidence: 98%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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“…In Drosophila , talin is not required to stabilize integrins on the cell surface or recruit them to muscle junctions. Instead, the major role of talin is to connect ECM bound integrins to the cytoskeleton [17], [41], [112], [62], [169]. Formation of microclusters has also been implicated in the function of integrin αLβ2.…”

Section: Talin-integrin Interactionmentioning

confidence: 99%

“…In Tln1 -/- embryonic fibroblasts, their adhesive phenotype was promoted only by an intact IBS-2 in talin-R [112]. At focal adhesions, only talin-R and not talin-H was observed [62]. In mammary epithelial cells, talin-R was found to be instrumental in recruiting FAK, vinculin and p21 to regulate cell proliferation [169].…”

Section: Talin and Integrin Outside-in Signalingmentioning

confidence: 99%

Mechanisms of talin-dependent integrin signaling and crosstalk

Das

Ithychanda

Qin

et al. 2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

111

103

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Cells undergo dynamic remodeling of the cytoskeleton during adhesion and migration on various extracellular matrix (ECM) substrates in response to physiological and pathological cues. The major mediators of such cellular responses are the heterodimeric adhesion receptors, the integrins. Extracellular or intracellular signals emanating from different signaling cascades cause inside-out signaling of integrins via talin, a cystokeletal protein that links integrins to the actin cytoskeleton. Various integrin subfamilies communicate with each other and growth factor receptors under diverse cellular contexts to facilitate or inhibit various integrin-mediated functions. Since talin is an essential mediator of integrin activation, much of the integrin crosstalk would therefore be influenced by talin. However, despite the existence of an extensive body of knowledge on the role of talin in integrin activation and as a stabilizer of ECM-actin linkage, information on its role in regulating inter-integrin communication is limited. This review will focus on the structure of talin, its regulation of integrin activation and discuss its potential role in integrin crosstalk.

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“…and the percentage of protein in the immobile fraction (IF) [24]. (I, II and IF refer to fractions of tethered, bound and immobile protein in adhesions, respectively; see Results).…”

Section: Resultsmentioning

confidence: 99%

The Vinculin-ΔIn20/21 Mouse: Characteristics of a Constitutive, Actin-Binding Deficient Splice Variant of Vinculin

et al. 2010

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BackgroundThe cytoskeletal adaptor protein vinculin plays a fundamental role in cell contact regulation and affects central aspects of cell motility, which are essential to both embryonal development and tissue homeostasis. Functional regulation of this evolutionarily conserved and ubiquitously expressed protein is dominated by a high-affinity, autoinhibitory head-to-tail interaction that spatially restricts ligand interactions to cell adhesion sites and, furthermore, limits the residency time of vinculin at these sites. To date, no mutants of the vinculin protein have been characterized in animal models.Methodology/Principal FindingsHere, we investigate vinculin-ΔEx20, a splice variant of the protein lacking the 68 amino acids encoded by exon 20 of the vinculin gene VCL. Vinculin-ΔEx20 was found to be expressed alongside with wild type protein in a knock-in mouse model with a deletion of introns 20 and 21 (VCL-ΔIn20/21 allele) and shows defective head-to-tail interaction. Homozygous VCL-ΔIn20/21 embryos die around embryonal day E12.5 showing cranial neural tube defects and exencephaly. In mouse embryonic fibroblasts and upon ectopic expression, vinculin-ΔEx20 reveals characteristics of constitutive head binding activity. Interestingly, the impact of vinculin-ΔEx20 on cell contact induction and stabilization, a hallmark of the vinculin head domain, is only moderate, thus allowing invasion and motility of cells in three-dimensional collagen matrices. Lacking both F-actin interaction sites of the tail, the vinculin-ΔEx20 variant unveils vinculin's dynamic binding to cell adhesions independent of a cytoskeletal association, and thus differs from head-to-tail binding deficient mutants such as vinculin-T12, in which activated F-actin binding locks the protein variant to cell contact sites.Conclusions/SignificanceVinculin-ΔEx20 is an active variant supporting adhesion site stabilization without an enhanced mechanical coupling. Its presence in a transgenic animal reveals the potential of splice variants in the vinculin gene to alter vinculin function in vivo. Correct control of vinculin is necessary for embryonic development.

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Control of High Affinity Interactions in the Talin C Terminus

Cited by 39 publications

References 45 publications

The tale of two talins – two isoforms to fine‐tune integrin signalling

The tale of two talins – two isoforms to fine‐tune integrin signalling

Mechanisms of talin-dependent integrin signaling and crosstalk

The Vinculin-ΔIn20/21 Mouse: Characteristics of a Constitutive, Actin-Binding Deficient Splice Variant of Vinculin

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