TRAF4 Is a Novel Phosphoinositide-Binding Protein Modulating Tight Junctions and Favoring Cell Migration

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration.     

The mechanism of insulin secretion following oral glucose administration. 4. Inhibition of the early reflectoric phase of plasma insulin increase through atropine]

In the first phase after on oral glucose load or after sham-feeding of glucose in conscious intact or on the oesophagus fistulated dogs respectively, the peripheral venous plasma insulin concentration increases independently of any blood glucose alteration. After previous intravenous atropin injection, this reflectoric insulin secretion cannot be observed. The N. vagus is involved in the afferent and/or efferent side of the reinforcing mechanism of insulin secretion basing on the entero-insular axis. Additionally the enteral glucose absorption is inhibited.     

X chromosome inactivation in 30 girls with Rett syndrome: Analysis using the probe

Rett syndrome (RS) is a neurologic disorder with an exclusive incidence in females. A nonrandom X-inactivation could provide insight into the understanding of this disease. We performed molecular analysis based on the differential methylation of the active and inactive X with probe M27ß, taking into account the parental origin of the two Xs, in 30 control girls, 8 sisters, and 30 RS girls. In 27 control an 31 RS mothers, the inactivation status of the X transmitted to their daughters was also analyzed. The results showed a significantly increased frequency of partial paternal X inactivation (> 65%) in lymphocytes from 16/30 RS compared with 4/30 controls (P = 0.001). These results do not support the hypothesis of a monogenic X-linked mutation but should be taken into account when researching the etiology of this desease.