Glucocorticoid Regulation of Astrocytic Fate and Function

Glial loss in the hippocampus has been suggested as a factor in the pathogenesis of stress-related brain disorders that are characterized by dysregulated glucocorticoid (GC) secretion. However, little is known about the regulation of astrocytic fate by GC. Here, we show that astrocytes derived from the rat hippocampus undergo growth inhibition and display moderate activation of caspase 3 after exposure to GC. Importantly, the latter event, observed both in situ and in primary astrocytic cultures is not followed by either early- or late-stage apoptosis, as monitored by stage I or stage II DNA fragmentation. Thus, unlike hippocampal granule neurons, astrocytes are resistant to GC-induced apoptosis; this resistance is due to lower production of reactive oxygen species (ROS) and a greater buffering capacity against the cytotoxic actions of ROS. We also show that GC influence hippocampal cell fate by inducing the expression of astrocyte-derived growth factors implicated in the control of neural precursor cell proliferation. Together, our results suggest that GC instigate a hitherto unknown dialog between astrocytes and neural progenitors, adding a new facet to understanding how GC influence the cytoarchitecture of the hippocampus

Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements

During the early stages of infection, Neisseria gonorrhoeae triggers a phosphotyrosine-dependent Cav1-Vav2-RhoA signaling cascade that promotes the pathogen's extracellular state

Crk and CrkL adaptor proteins: networks for physiological and pathological signaling

The Crk adaptor proteins (Crk and CrkL) constitute an integral part of a network of essential signal transduction pathways in humans and other organisms that act as major convergence points in tyrosine kinase signaling. Crk proteins integrate signals from a wide variety of sources, including growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic cells. Mounting evidence indicates that dysregulation of Crk proteins is associated with human diseases, including cancer and susceptibility to pathogen infections. Recent structural work has identified new and unusual insights into the regulation of Crk proteins, providing a rationale for how Crk can sense diverse signals and produce a myriad of biological responses

I did it my way: Voice, visuality and identity in doctoral students’ reflexive videonarratives on their doctoral research journeys

This paper presents four accounts of UK doctoral students’ engagement in a Higher Education Academy project which used digital video to promote participants’ reflexivity on their doctoral journeys. It focuses on the relations between doctoral research, reflexivity and the use of digital video, and how these relations are articulated in different ways by the project participants in the production of, and reflection on, their own videonarrative. As an ‘assemblage’, the written form of the paper aims to evoke both the collaborative design of the project, in that the paper is constructed as a multivocality, a series of ‘plateaus’ (Deleuze and Guattari, 1987, p22), and also the multiple, shifting and always in-process nature of identity, immanent in each individual’s account. In different ways, the accounts address how epistemological, ontological and ethical considerations are articulated within a visual and vocal re-presentation of the self in the form of individual videonarratives. Each narrative both does (and doesn’t) resonate with the others’ narratives and each offers unique insights into the specificities of a particular doctoral journey. In experimenting with this form of presentation, the aim is to bypass traditional accounts of research ‘findings’ as a form of transparent knowledge production and, instead, work within a mode of representation which seeks to acknowledge what Lather (2007, p119) calls the ‘masks of methodology’. Keywords: voice, visuality, identity, doctoral students, reflexivity, videonarrativ

Abl tyrosine kinases regulate cell–cell adhesion through Rho GTPases

Adherens junctions are calcium-dependent cell–cell contacts that link neighboring cells through cadherin receptors. Coordinated regulation of the actin cytoskeleton by the Rho GTPases is required for the formation and dissolution of adherens junctions. However, the pathways that link cadherin signaling to cytoskeletal regulation remain poorly defined. Here we identify the Abl family kinases as critical mediators of cadherin-mediated adhesion. Endogenous Abl family kinases, Abl and Arg, are activated and required for Rac activation after cadherin engagement and regulate the formation and maintenance of adherens junctions in mammalian cells. Significantly, we show that Abl-dependent regulation of the Rho–ROCK–myosin signaling pathway is critical for the maintenance of adherens junctions. Inhibition of the Abl kinases in epithelial sheets results in the activation of Rho and its downstream target ROCK, leading to enhanced phosphorylation of the myosin regulatory light chain. These signaling events result in enhanced stress fiber formation and increased actomyosin contractility, thereby disrupting adherens junctions. Conversely, Arg gain of function promotes adherens junction formation through a Crk-dependent pathway in cells with weak junctions. These data identify the Abl kinases as a regulatory link between the cadherin–catenin adhesion complex and the actin cytoskeleton through regulation of Rac and Rho during adherens junction formation, and also reveal a functional link between Abl and Rho that is essential for adherens junction stability

Abl Tyrosine Kinase Phosphorylates Nonmuscle Myosin Light Chain Kinase to Regulate Endothelial Barrier Function

This study identified multiple novel c-Abl–mediated nmMLCK phosphorylation sites by mass spectroscopy and examined their influence on nmMLCK function and human lung endothelial barrier regulation. The data indicate an essential role for Abl kinase in vascular barrier regulation via phosphorylation of nmMLCK and the actin-binding protein cortactin