Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol

Abstract

How can the integrin adhesome get self-assembled locally, rapidly, and correctly as diverse cell-matrix adhesion sites? Here, we investigate this question by exploring the cytosolic state of integrin-adhesome components and their dynamic exchange between adhesion sites and cytosol. Using fluorescence cross-correlation spectroscopy (FCCS) and fluorescence recovery after photobleaching (FRAP) we found that the integrin adhesome is extensively pre-assembled already in the cytosol as multi-protein building blocks for adhesion sites. Stationary focal adhesions release symmetrically the same types of protein complexes that they recruit, thereby keeping the cytosolic pool of building blocks spatiotemporally uniform. We conclude a model in which multi-protein building blocks enable rapid and modular self-assembly of adhesion sites and symmetric exchange of these building blocks preserves their specifications and thus the assembly logic of the system.DOI: http://dx.doi.org/10.7554/eLife.02257.001

IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover

“…(legend on next page) on integrin endocytosis for their proper turnover at MASs has been reported , while recent findings have shown that focal adhesion-interacting proteins display similar kinetics (Hoffmann et al, 2014). Thus, the talin-GFP exchange rate is increased in Parvin mutants; however, the mys b58 GOF allele is sufficient to restore it.…”

Early Events in Cell Spreading as a Model for Quantitative Analysis of Biomechanical Events

“…In contrast, individual proteins exchange between the adhesion and cytoplasm within seconds, highlighting the dynamic nature of the adhesion (26,69,70). Again, the exchange rates correlate with myosin forces, and many critical components exchange more slowly and less extensively in the presence of blebbistatin (e.g., paxillin), whereas others exchange more readily (e.g., vinculin) (26).…”

Emerging properties of adhesion complexes: what are they and what do they do?

“…By contrast, candidate-based microscopy studies have focused on the architecture, interactions, and dynamics of adhesion complex assembly and disassembly [34,36,37]. For example, recent studies have identified that many adhesome components are pre-assembled as multi-protein building blocks in the cytosol, allowing rapid adhesion complex maturation and turnover [34]. Together these studies have contributed to our understanding of integrin signalling, force generation, and actin regulation and their impact on numerous downstream cellular processes.…”

“…Proteomic analyses also suggest the existence of a large number of non-canonical adhesome components. By contrast, candidate-based microscopy studies have focused on the architecture, interactions, and dynamics of adhesion complex assembly and disassembly [34,36,37]. For example, recent studies have identified that many adhesome components are pre-assembled as multi-protein building blocks in the cytosol, allowing rapid adhesion complex maturation and turnover [34].…”