The Role of Actin-binding Protein 280 in Integrin-dependent Mechanoprotection

Abstract

To survive in a mechanically active environment, cells must adapt to variations of applied membrane tension. A collagen-coated magnetic bead model was used to apply forces directly to the actin cytoskeleton through integrin receptors. We demonstrate here that by a calcium-dependent mechanism, human fibroblasts reinforce locally their connection with extracellular adhesion sites by inducing actin assembly and by recruiting actinbinding protein 280 (ABP-280) into cortical adhesion complexes. ABP-280 was phosphorylated on serine residues as a result of force application. This phosphorylation and the force-induced actin reorganization were largely abrogated by inhibitors of protein kinase C. In a human melanoma cell line that does not express ABP-280, actin accumulation could not be induced by force, whereas in stable transfectants expressing ABP-280, force-induced actin accumulation was similar to human fibroblasts. Cortical actin assembly played a role in regulating the activity of stretch-activated, calcium-permeable channels (SAC) since sustained force application desensitized SAC to subsequent force applications, and the decrease in stretch sensitivity was reversed after treatment with cytochalasin D. ABP-280-deficient cells showed a >90% increase in cell death compared with ABP-280؉ve cells after force application. We conclude that ABP-280 plays an important role in mechanoprotection by reinforcing the membrane cortex and desensitizing SACs.

Mechanoregulation of gene expression in fibroblasts

“…Previous studies have suggested that mechanical force application to integrins can activate mechanosensitive ion channels and trigger Ca 2+ entry into cells. Ca 2+ entry may influence cell mechanics by modulating cytoskeletal structure or contractility (Glogauer et al, 1997(Glogauer et al, , 1998. Ca 2+ -activated proteases, such as calpain are associated with FAs (Glading et al, 2002).…”

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

“…Outside the nervous system, one of the most prominent editing-induced recoding events occurs in filamins. Filamins are actin-binding proteins which link the actin network to cellular membranes and transmembrane receptors [9]. The interactions with a plethora of proteins link filamins to different cellular processes, such as signalling, transcriptional regulation, migration, and tissue organization [10].…”

Development of a device to stretch tissue-like materials and to measure their mechanical properties by scanning probe microscopy

“…First, it may be due to an elastic response of the actin filaments [25]; second, it may be attributed to the changes in the cellular activities such as enhancement of the contractile force and reinforcement of stress fibers [10,26]. Janmey et al investigated the elastic property of an actin matrigel and showed that more than 10% of the strain was required to yield a 2-fold increase in stress [27].…”