CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis and adhesion site turnover

Stehbens, Samantha J.; Paszek, Matthew J.; Pemble, Hayley; Ettinger, Andreas; Gierke, Sarah; Wittmann, Torsten

doi:10.1038/ncb2975

Cited by 226 publications

(283 citation statements)

References 61 publications

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“…We confirmed these results both in HeLa cells and the HaCaT immortal keratinocyte cell line, in which CMSC components CLASPs and LL5b were previously shown to strongly cluster around FAs and regulate their turnover during cell migration (Stehbens et al, 2014) (Figure 1-figure supplement 1A,B). Inhibition of myosin-II with blebbistatin, which reduces tension on the actin fibers and affects the activation state of FA molecules, such as integrins and talin (Parsons et al, 2010), caused not only FA disassembly but also a strong reduction in clustering of CMSC components at the cell periphery ( Figure 1-figure supplement 2A,B), as described previously (Stehbens et al, 2014). To investigate this effect in more detail, we partially inhibited contractility using a Rho-associated protein kinase 1 (ROCK1) inhibitor, Y-27632 (Oakes et al, 2012).…”

Section: Identification Of Talin1 As a Kank1 Binding Partnersupporting

confidence: 73%

“…In migrating keratinocytes, LL5b and CLASPs accumulate around FAs and promote their disassembly by targeting the exocytosis of matrix metalloproteases to FA vicinity (Stehbens et al, 2014). Furthermore, liprin-a1, LL5a/b and ELKS localize to protrusions of human breast cancer cells and are required for efficient cell migration and FA turnover (Astro et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

108

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The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote the cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5b and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule-stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules.

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Section: Identification Of Talin1 As a Kank1 Binding Partnersupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

Bouchet

Gough

Willige

et al. 2016

Preprint

108

View full text Add to dashboard Cite

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“…The microtubule-associated proteins CLASP1 and CLASP2 were identified as the tethering factors that actually link microtubules to focal adhesions thereby establishing a focal adhesion directed transport pathway, e.g. for the delivery and localized fusion of exocytic vesicles secreting proteases involved in extracellular matrix degradation [89]. Thus, microtubules may serve here to establish a local secretion pathway that facilitates focal adhesion turnover by severing cell matrix connections.…”

Section: Focal Adhesion Disassemblymentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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“…The histogram and the log-logistic curve fit of the lifetime distribution was calculated in MAT LAB (MathWorks). Kymographs were generated from the "Show Slices View" in NIS Elements by building a stack of y-t views and displaying a maximum-intensity projection of 3-4 y-t views to suppress image noise essentially as described (Stehbens et al, 2014). Final figures were assembled in Illustrator CS5 (Adobe).…”

Section: ° Light Scatteringmentioning

confidence: 99%