Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions

Chicurel, Marina; Singer, Robert H.; Meyer, Christian J.; Ingber, Donald E.

doi:10.1038/33719

Cited by 345 publications

(246 citation statements)

References 29 publications

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“…As activated forms of signalling proteins such as focal adhesion kinase (FAK), Src, p130Cas, integrin-linked kinase (ILK), and Erk are clustered in cell-matrix adhesions [18,19], signal transduction may be strongly amplified at these sites. Moreover, even mRNA and ribosomes [20] can be found in these adhesions, suggesting that they may locally connect signal transduction to protein synthesis.…”

Section: Mechanisms Of Integrin Signallingmentioning

confidence: 99%

Integrins in regulation of tissue development and function

Danen¹,

Sonnenberg²

2003

The Journal of Pathology

230

173

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Cell adhesion is indispensable for embryonic development and for proper tissue function. In metazoans, integrins are the major adhesion receptors that connect cells to components of the extracellular matrix. Integrins are implicated in assembly of extracellular matrices, cell adhesion and migration on extracellular matrices, and in vertebrates (in which the integrin family has expanded) they can also mediate cell-cell adhesion. Furthermore, integrinmediated adhesion can modulate many different signal transduction cascades and support cell survival, proliferation, and influence the expression of differentiation-related genes. In this review we briefly explain how integrins can affect so many different aspects of cell behavior and discuss evidence for roles of integrins in tissue development, function, and disease.

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Section: Mechanisms Of Integrin Signallingmentioning

confidence: 99%

Integrins in regulation of tissue development and function

Danen¹,

Sonnenberg²

2003

The Journal of Pathology

230

173

View full text Add to dashboard Cite

show abstract

“…64 Integrins require an immobilized substrate ligand (or other tensional force) to promote sustained signaling and cytoskeletal remodeling. Thus, although the presence of a soluble netrin may be sufficient to promote survival of cells expressing the dependence receptor DCC, 65 soluble integrin ligands are generally insufficient to maintain cell survival, and instead tend to act as antagonists which prevent engagement of substrate ligands, thus promoting integrin-mediated death.…”

Section: Antagonized Integrins Promote Apoptosis Of Adherent Cellsmentioning

confidence: 99%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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In the absence of their cognate ligand, dependence receptors trigger programmed cell death. This function is the defining feature of dependence receptors, which include members of several different protein families. The integrins are a family of heterodimeric receptors for extracellular matrix (ECM) proteins, mediating cell anchorage and migration. Integrins share characteristics with dependence receptors, and integrin binding to substrate ECM ligands is essential for cell survival. Although integrins do not conform in all characteristics to the established definitions of dependence receptors, alterations in the expression of integrins and their ligands during physiological and pathological events, such as wound healing, angiogenesis and tumorigenesis, do regulate cell fate in a ligand-dependent manner. This biosensory function of integrins fits well with our current concept of dependence receptor action, and thus integrins may rightly be considered to comprise a distinct subclass of dependence receptor.

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“…Our laboratory has previously demonstrated that twisting magnetic microbeads bound to ligated integrin receptors increases signaling through cAMP in a stress-dependent manner, whereas twisting other transmembrane receptors on the same cell (e.g., metabolic receptors and histocompatibility antigens) has no effect [14], [15]. In the current study, our goal was to leverage cAMP signaling through integrins to develop techniques for magnetic control of signal transduction and gene transcription in living mammalian cells that may be applied in the future toward the development of cell-based microtechnologies.…”

Section: Resultsmentioning

confidence: 99%

“…This mechanical coupling is responsible for changes in cell mechanics (e.g., strainhardening behavior) that are observed when cells are mechanically stressed [4], [10]. Focal adhesions also contain multiple proteins involved in biochemical signaling [8], [11]- [13] that act to transduce mechanical stress applied to integrins into biochemical responses that affect signal transduction and gene expression [14]- [17].…”

Section: Introductionmentioning

confidence: 99%

Magnetic Cellular Switches

et al. 2004

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This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcription of these gene reporters by applying magnetic (mechanical) stress to magnetic microbeads bound to cell surface integrin receptors. In these gene reporter constructs, CRE motifs drive the expression of fluorescent proteins or enzymes that produce fluorescent products, such as DsRed and β-lactamase (BLA), respectively. We demonstrate that a chemical inducer of cAMP (forskolin) increases expression of CRE-DsRed in living cells. More importantly, a threefold increase in CRE-BLA expression is induced by application of mechanical stress to magnetic microbeads (4.5 µm) bound to cell surface integrin receptors. Induction of cAMP could be detected within 5 min using a protein fragment complementation assay involving interactions between the KID and KIX domains of the CRE binding protein linked to complementary halves of the BLA enzyme. These studies confirm that application of magnetic stress to integrins induces gene transcription by activating the cAMP-dependent transcription factor CREB. Ongoing studies focus on optimizing sensitivity and reducing signal-to-noise by establishing stable cell lines that express these gene reporters. These studies collectively demonstrate the feasibility of using magnetic technologies to control function in living mammalian cells and, hence, support the possibility of developing magnetically-actuated cellular components for use in future micro-and nanotechnologies.

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Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions

Cited by 345 publications

References 29 publications

Integrins in regulation of tissue development and function

Integrins in regulation of tissue development and function

Integrins as a distinct subtype of dependence receptors

Magnetic Cellular Switches

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