A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.

Diseases caused by mutations in lamins A and C (laminopathies) suggest a crucial role for A-type lamins in different cellular processes. Laminopathies mostly affect tissues of mesenchymal origin. As transforming growth factor-beta1 (TGF-beta1) signalling impinges on the retinoblastoma protein (pRB) and SMADs, we tested the hypothesis that lamins modulate cellular responses to TGF-beta1 signalling, via the regulation of these transcription factors in mesenchymal cells. Here, we report that A-type lamins are essential for the inhibition of fibroblast proliferation by TGF-beta1. TGF-beta1 dephosphorylated pRB through PP2A, both of which, we show, are associated with lamin A/C. In addition, lamin A/C modulates the effect of TGF-beta1 on collagen production, a marker of mesenchymal differentiation. Our findings implicate lamin A/C in control of gene activity downstream of TGF-beta1, via nuclear phosphatases such as PP2A. This biological function provides a novel explanation for the observed mesenchymal dysfunction in laminopathie

Social rejection in social anxiety disorder:the role of performance deficits, evoked negative emotions and dissimilarity

Objectives. Patients with social anxiety disorder (SAD) not only fear social rejection, but accumulating evidence also shows that they are indeed less liked than their non-anxious counterparts. Three factors are hypothesized to play a role in this social anxiety-social rejection relationship: (1) social performance; (2) elicited negative emotions, and (3) perceived similarity. Method. Patients with SAD (N = 63) and control participants (N = 27) were observed during a 5 minutes 'getting acquainted' conversation with a male and female confederate who rated their social performance. Video-observers rated their own negative emotions and perceived similarity with the patients, while other video-observers rated their wish to engage in future contact with them (a measure of social rejection). Results. Analysed by way of structural equation modelling (SEM), the results supported the social anxiety-social rejection relationship. More specifically, poor social performance was associated with perceived dissimilarity ratings and mediated by evoked negative emotions, both of which were in turn associated with social rejection. Conclusion. These results suggest that a sequence of events links social anxiety to social rejection. Treatment should aim to improve social performance and perceived similarity to reverse SAD's vicious, negative interpersonal cycle