The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus

BACKGROUND: At sites of cell adhesion, proteins exist that not only perform structural tasks but also have a signaling function. Previously, we found that the Lipoma Preferred Partner (LPP) protein is localized at sites of cell adhesion such as focal adhesions and cell-cell contacts, and shuttles to the nucleus where it has transcriptional activation capacity. LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. LPP has three LIM domains (zinc-finger protein interaction domains) at its carboxy-terminus, which are preceded by a proline-rich pre-LIM region containing a number of protein interaction domains. RESULTS: To catch the role of LPP at sites of cell adhesion, we made an effort to identify binding partners of LPP. We found the tumor suppressor protein Scrib, which is a component of cell-cell contacts, as interaction partner of LPP. Human Scrib, which is a functional homologue of Drosophila scribble, is a member of the leucine-rich repeat and PDZ (LAP) family of proteins that is involved in the regulation of cell adhesion, cell shape and polarity. In addition, Scrib displays tumor suppressor activity. The binding between Scrib and LPP is mediated by the PDZ domains of Scrib and the carboxy-terminus of LPP. Both proteins localize in cell-cell contacts. Whereas LPP is also localized in focal adhesions and in the nucleus, Scrib could not be detected at these locations in MDCKII and CV-1 cells. Furthermore, our investigations indicate that Scrib is dispensable for targeting LPP to focal adhesions and to cell-cell contacts, and that LPP is not necessary for localizing Scrib in cell-cell contacts. We show that all four PDZ domains of Scrib are dispensable for localizing this protein in cell-cell contacts. CONCLUSIONS: Here, we identified an interaction between one of zyxin's family members, LPP, and the tumor suppressor protein Scrib. Both proteins localize in cell-cell contacts. This interaction links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates LPP in Scrib-associated functions

Lung Function of Infants with Congenital Lung Lesions in the First Year of Life

Item does not contain fulltextBackground: Several studies have evaluated short-term neonatal outcome in infants with congenital lung lesions (CLL) but clinical course and lung function in the longer term have not yet been documented. We hypothesized that clinical course and lung function would be negatively affected by surgical resection. Objective: To evaluate respiratory symptoms and lung function longitudinally in the first year of life in infants with CLL, and to analyse differences herein between infants managed by observation only and infants whose affected lung parts were resected. Methods: We evaluated respiratory symptoms and lung function at 6 and 12 months in 30 patients with CLL. Functional residual capacity (FRC(p)) and maximal expiratory flow at functional residual capacity (V'(max)FRC) were measured with body plethysmography. SD scores were calculated for V'(max)FRC. Results: Prevalence of respiratory symptoms did not differ between the groups. Mean FRC(p) (95% CI) was 25.3 (23.3-27.3) in the group managed by observation versus 27.3 (25.1-29.6) in the group managed by surgery (p = 0.149). Mean (95% CI) SDS V'(max)FRC was -1.45 (-1.84 to -1.06) versus -1.41 (-1.90 to -0.91) (p = 0.892). Lung function did not change significantly over the 6-month period. Conclusion: Surgical resection did not seem to have negatively affected the clinical course and lung function. We recommend pulmonary follow-up of all CLL patients into adulthood to further identify any long-term effects of CLL and observation or surgery