Metabolic syndrome, leaky guts, and infection: Metabolic syndrome often accompanies obesity and hyperglycemia and is associated with a breakdown in the integrity of the intestinal barrier and increased risk of systemic infection. Thaiss et al. found that mice with systemic infection of a Salmonella analog, Citrobacter rodentium , also exhibited hyperglycemia. Deletion of the glucose transporter GLUT2 altered sensitivity to chemically induced epithelial permeability and protected mice from pathogen invasion. The authors also found a correlation in humans between glycated hemoglobin (an indicator of hyperglycemia) and serum levels of pathogen recognition receptor ligands. Science , this issue p. 1376

Currently >50 proteins have been reported to be associated with focal contacts and related ECM adhesions. Most of these contain multiple domains through which they can interact with different molecular partners, potentially forming a dense and heterogeneous protein network at the cytoplasmic faces of the adhesion site. The molecular and structural diversity of this ‘submembrane plaque’ is regulated by a wide variety of mechanisms, including competition between different partner proteins for the same binding sites, interactions triggered or suppressed by tyrosine phosphorylation, and conformational changes in component proteins, which can affect their reactivity. Indeed, integrin-mediated adhesions can undergo dynamic changes in structure and molecular properties from dot-like focal complexes to stress-fiber-associated focal contacts, which can further ‘mature’ to form fibronectin-bound fibrillar adhesions. These changes are driven by mechanical force generated by the actin- and myosin-containing contractile machinery of the cells, or by external forces applied to the cells, and regulated by matrix rigidity.

Cellular locomotion is driven by repeated cycles of protrusion of the leading edge, formation of new matrix adhesions and retraction of the trailing edge. In this study we addressed the molecular composition and dynamics of focal complexes, formed under the leading lamellae of motile cells, and their maturation into focal adhesions. We combined phase-contrast and fluorescence microscopy approaches to monitor the incorporation of phosphotyrosine and nine different focal adhesion proteins into focal complexes in endothelial cells, migrating into an in vitro `wound9. We show that newly formed complexes are located posterior to an actin-, VASP- and α-actinin-rich region in the lammelipodium. They are highly tyrosine phosphorylated, contain β₃-integrin, talin, paxillin and low levels of vinculin and FAK, but are apparently devoid of zyxin and tensin. The recruitment of these proteins into focal complexes occurs sequentially, so that their specific protein composition depends on their age. Interestingly, double color, time-lapse movies visualizing both paxillin and zyxin, indicated that the transition from paxillin-rich focal complexes to definitive, zyxin-containing focal adhesions, takes place only after the leading edge stops advancing or retracts. These observations illuminate, for the first time, early stages in focal complex assembly and the dynamic process associated with its transformation into focal adhesion.