Cell-extracellular matrix adhesion is an important determinant of cell morphology. We show here that migfilin, a LIM-containing protein, localizes to cell-matrix adhesions, associates with actin filaments, and is essential for cell shape modulation. Migfilin interacts with the cell-matrix adhesion protein Mig-2 (mitogen inducible gene-2), a mammalian homolog of UNC-112, and the actin binding protein filamin through its C- and N-terminal domains, respectively. Loss of Mig-2 or migfilin impairs cell shape modulation. Mig-2 recruits migfilin to cell-matrix adhesions, while the interaction with filamin mediates the association of migfilin with actin filaments. Migfilin therefore functions as an important scaffold at cell-matrix adhesions. Together, Mig-2, migfilin and filamin define a connection between cell matrix adhesions and the actin cytoskeleton and participate in the orchestration of actin assembly and cell shape modulation.

Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with ␤1 and ␤3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using ␣IIb␤3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.Cell-extracellular matrix (ECM) 3 adhesion is a fundamental process that is mediated by transmembrane receptors such as integrins (1-6). The interactions of integrins with ECM ligands can be controlled by integrin activation via "inside-out" signaling. Talin, a FERM (Band 4.1 (four point one)/ezrin/radixin/ moesin) domain-containing focal adhesion (FA) protein, can play a key role in this process (for recent reviews, see Refs. 7-10). Binding of the talin FERM domain to the ␤ integrin cytoplasmic domains results in separation of the ␣ and ␤ integrin cytoplasmic tails and consequently in an increase in integrin extracellular ligand-binding affinity (i.e. integrin activation) (11-13). Integrin extracellular ligand-binding affinity plays an important role in control of initial cell-ECM adhesion. Additionally, integrin-mediated cell-ECM adhesion can be enhanced through interactions with cytoskeletal proteins, a process that has been termed cytoskeletal strengthening (14 -16). The physical basis underlying the cytoskeletal strengthening of cell-ECM adhesion has been well described (16). However, the molecular interactions that mediate this process remain to be defined.MIG-2 (mitogen-inducible gene-2, also known as kindlin-2) is a widely expressed and evolutionarily conserved cytoplasmic protein (17-21). Genetic studies have shown that Caenorhabditis elegans UNC-112, a homolog of MIG-2, is required for attachment of body-wall muscle cells to the hypodermis (17,19). Loss of UNC-112 in C. elegans results in an embryonic lethal Pat (paralyzed, arrested elongation at two-fold) phenotype resembling that of ␣ or ␤ integrin loss (17, 19). In mammalian organisms, MIG-2 has been detected in many cell types, including fibroblasts, muscle cells, endothelial cells, and epithelial cells (20,22). In these cells, it concentrates at FAs. MIG-2 interacts with migfilin (20), a filamin-and VASP (vasodilatorstimulated p...

Heart disease is among the leading causes of death in all populations. Cardiac dysfunctions are major complications in patients with advanced viral or bacterial infection, severe trauma and burns accompanied with multiple organ failure - collectively known as systemic inflammatory response syndrome (SIRS). SIRS, which is often subsequent to sepsis, is clinically featured by hypotension, tachypnea, hypo- or hyperthermia, leukocytosis and myocardial dysfunction. The striking association between inflammation and cardiac dysfunction not only prognoses likelihood of survival in patients with SIRS but also prompts the necessity of understanding the pathophysiology of cardiac dysfunction in SIRS, so that effective therapeutic regimen may be identified. Compelling evidence has shown significant and independent link among inflammation, sepsis, insulin resistance and cardiac dysfunction. Several cytokine signaling molecules have been speculated to play important roles in the onset of cardiac dysfunction under SIRS including endothelin-1 and toll-like receptor. Involvement of these pathways in cardiac dysfunction has been convincingly validated with transgenic studies. Nevertheless, the precise mechanism of action underscoring inflammation-induced cardiac contractile dysfunction is far from being clear. Given the substantial impact of inflammation and SIRS on health care, ecosystems and national economy, it is imperative to understand the cellular mechanisms responsible for cardiac contractile dysfunction under inflammation and sepsis so that new and effective therapeutic strategy against such devastating heart problems may be developed.

We study how career concerns influence banking analysts' forecasts and how their forecasting behavior benefits both them and bank managers. We show that banking analysts issue early in the year relatively more optimistic and later in the year more pessimistic forecasts for banks that could be their future employers. This pattern is not observed when the same analysts forecast earnings of companies that are not likely to be their future employers. Moreover, we use the Global Settlement as an exogenous shock, which limited outside opportunities and therefore exacerbated career concerns, and show that this forecast pattern is more pronounced after the Settlement. Both analysts and bank executives benefit from this behavior. Analysts issuing more biased forecasts for potential future employers are more likely to face favorable career outcomes and bank executives appear to profit from the analysts bias since the bias is associated with higher levels of insider trading. Our results highlight the bias created by asking analysts to rate their outside opportunities in the labor market.JEL Classification: G14, G24, G28, G32

N-Methyl-D-aspartate (NMDA) receptors are implicated in a wide range of complex behavioral functions, including cognitive activity. Numerous studies have shown that using the repetitive administration of a noncompetitive NMDA receptor antagonist, MK-801, induces amnesia in rodents. In this study, the effect of a subchronic MK-801 treatment on the cognitive function of zebrafish was evaluated using a novel inhibitory avoidance task. First, we established a new system to investigate the inhibitory avoidance learning of zebrafish where they were trained to refrain from swimming from a shallow compartment to a deep compartment in order to avoid electric shock. Second, we found that blocking NMDA receptors by MK-801 could significantly attenuate the inhibitory avoidance behavior of the zebrafish and alter the telencephalic extracellular signal-regulated kinase (ERK) phosphorylation level 90 min after the inhibitory avoidance training. These results suggest that the formation of long-term emotional memory is possibly mediated by ERK activation in the telencephalon of zebrafish.