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ConFERMing the role of talin in integrin activation and mechanosignaling

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CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry

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The C-terminal actin-binding domain of talin forms an asymmetric catch bond with F-actin

Leanna M. Owen et al.

Summary: This study found that talin ABS3 forms long-lived catch bonds with F-actin under force, which is necessary for normal focal adhesion formation. The results support a mechanism in which talin ABS3 preferentially binds to and orients actin filaments, leading to long-range order in the actin cytoskeleton. Talin ABS3 may serve as a molecular AND gate that allows focal adhesion growth only when sufficient integrin density, F-actin polarization, and mechanical tension are simultaneously present.

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Mechanism of integrin activation by talin and its cooperation with kindlin

Fan Lu et al.

Summary: The authors report a mechanism in which talin and kindlin are bridged by paxillin to induce microclustering of integrins, leading to potent binding between integrins and extracellular ligands. The study also reveals that the C-terminal rod domain of talin enhances its potency in activating integrins by dimerizing activated talin and bridging it to the integrin co-activator kindlin-2 via paxillin. This study provides crucial insights into the mechanism of talin and its cooperation with kindlin in promoting integrin activation and cell adhesion.

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Paxillin: A Hub for Mechano-Transduction from the β3 Integrin-Talin-Kindlin Axis

Marta Ripamonti et al.

Summary: Focal adhesions are cell structures that anchor cells to the extracellular matrix and also play a role in mechanosignaling by integrating physical and chemical cues from the microenvironment. Paxillin, a protein involved in focal adhesion formation and scaffolding, appears to have a key role in integrating multiple signals and activating various molecular responses from the microenvironment. This minireview provides an overview of the molecular mechanisms underlying the mechanosensitivity and mechanosignaling capacity of core focal adhesion proteins, with a focus on the role of paxillin.

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Mechanical regulation of talin through binding and history-dependent unfolding

Narayan Dahal et al.

Summary: The study found that the R8 domain of talin displays memory-dependent behavior under force, indicating the evolution of a unique force-induced native state. It was also discovered that talin R8 domain binds its ligand DLC1 with much higher affinity than previously reported. This interaction may explain the anti-tumor response of DLC1 by regulating the inside-out activation of integrins.

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Structural Basis of β2 Integrin Inside-Out Activation

Lai Wen et al.

Summary: This article focuses on the precise regulation of beta 2 integrin and the role of talin-1 and kindlin-3 in this process. When activated, talin-1 and kindlin-3 can bind to the cytoplasmic tail of beta 2 integrin, playing a crucial role in integrin activation. The study proposes a new model for the final steps of integrin activation involving the complex of talin-1, kindlin-3, integrin, and the plasma membrane.
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Phosphorylation of RIAM by src promotes integrin activation by unmasking the PH domain of RIAM

Eun-Ah Cho et al.

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Cancer associated talin point mutations disorganise cell adhesion and migration

Latifeh Azizi et al.

Summary: The study identified the potential impact of cancer-related point mutations in talin-1 on cell behavior and cancer progression. By analyzing mutations, developing prediction pipelines, and conducting experiments, the study provides insights into the functional effects and pathogenicity of talin-1 mutants.

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Talin in mechanotransduction and mechanomemory at a glance

Benjamin T. Goult et al.

Summary: Talins are cytoskeletal linker proteins with a head domain, neck region, and a rod domain. The head domain binds integrin beta-subunit cytoplasmic tails to increase affinity for extracellular matrix proteins. The rod domain links to actin filaments to transmit mechanical loads and functions as a mechanosensitive signaling hub.

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Quantitative single-protein imaging reveals molecular complex formation of integrin, talin, and kindlin during cell adhesion

Lisa S. Fischer et al.

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Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions

Marta Ripamonti et al.

Summary: The study provides insights into the molecular organization of beta 3 integrin-FAs, showing the specific contributions of individual Paxillin LIM domains in targeting and maintaining the structural integrity of focal adhesions (FAs). Ripamonti et al. demonstrate the importance of mechanical coupling of paxillin in the FA to the plasma membrane or integrin for FA stability and integrin-talin linkage.

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Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1

Rosemarie E. Gough et al.

Summary: Talin is a key component that connects integrins to the actin cytoskeleton in adhesion complexes. CDK1 maintains adhesion during interphase and directly interacts with talin at integrin-mediated adhesion sites. This coupling between CDK1 and talin suggests a mechanism by which the microenvironment can regulate cell division in multicellular organisms.

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Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions

Thomas Orre et al.

Summary: Focal adhesions (FAs) play a key role in initiating chemical and mechanical signals for cell polarity, migration, proliferation, and differentiation. The study integrates single protein tracking, super-resolution microscopy, and functional assays to correlate the molecular behavior and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs. This research provides insights into the molecular mechanisms underlying the interaction of kindlin with integrins in focal adhesions.

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Myosin-X and talin modulate integrin activity at filopodia tips

Mitro Miihkinen et al.

Summary: Active integrins accumulate at the tip of myosin-X (MYO10)-positive filopodia, while inactive integrins are uniformly distributed. MYO10 and talin are identified as the principal integrin activators in filopodia. Experimental results show that MYO10 facilitates integrin activation in filopodia, rather than transport.

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Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking

Thomas Bromberger et al.

Summary: Beta 2 integrins play a crucial role in leukocyte trafficking by mediating the processes of slow rolling and firm arrest through conformational changes, which are regulated by interactions with Rap1 and Riam. The loss of both pathways simultaneously results in a rolling phenotype similar to talin1 deficient neutrophils, suggesting that these two pathways primarily regulate beta 2 integrin.

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