Functional Bioinformatics Analyses of the Matrisome and Integrin Adhesome.

The extracellular matrix (ECM) is the noncellular compartment of living organisms and is formed of a complex network of cross-linked proteins, which is collectively known as the matrisome. Apart from providing the structure for an organism, cells interact and thereby communicate with the ECM. Cells interact with their surrounding ECM using cell-surface receptors, such as integrins. Upon integrin engagement with the ECM, cytoskeletal proteins are recruited to integrins and form a molecular protein complex known as the integrin adhesome. Global descriptions of the matrisome and integrin adhesome have been proposed using in silico bioinformatics approaches, as well as through biochemical enrichment of matrisome and adhesome fractions coupled with mass spectrometry-based proteomic analyses, providing inventories of their compositions in different contexts. Here, methods are described for the computational downstream analyses of matrisome and adhesome mass spectrometry datasets that are accessible to wet lab biologists, which include comparing datasets to in silico descriptions, generating interaction networks and performing functional ontological analyses.

Prediction study on signal transduction pathways of integrin adhesome / 医用生物力学

Objective To predict signal transduction pathways of the integrin adhesome via bioinformatics method, so as to provide references for experimental study on the mechanism of integrin-related signal transduction pathways. Methods First, the interaction network between the interactive integrin adhesome was constructed, and the confidence probability of each interaction was used as its link weight, respectively. Secondly, the pathways of the minimum weight were identified via a standard dynamic programming algorithm. Finally, all pathways calculated by the algorithm were aggregated into some probable networks. Results Seven signal transduction pathways were obtained from the integrin adhesome interaction network that contained 147 components with 736 interactions. In every predicted signal transduction pathway, the coverage rate of the proteins with Gene Ontology annotation was calculated. Conclusions By research on signal transduction pathways the pathogenesis of some diseases can be explored at the molecular level. Several possible signal transduction pathways obtained in this study have some reference value for exploring disease mechanism in basic medical sciences, and also provide some useful information for such exploration under the stimulation of external signals including mechanical or chemical signals.

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

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.