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

Marleen Mr Petit,Erik Jansen,Torik Ay Ayoubi,Sandra Mp Meulemans,Wim Jm Van De Ven,Philippe Alen

doi:10.1186/1471-2121-6-1

Marleen Mr Petit, Erik Jansen + Show 4 more

Open Access

https://doi.org/10.1186/1471-2121-6-1

Copy DOI

Abstract

BackgroundAt 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.ResultsTo 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.ConclusionsHere, 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.

Highlights

At sites of cell adhesion, proteins exist that perform structural tasks and have a signaling function
Screening for Lipoma Preferred Partner (LPP)-interacting proteins by yeast two-hybrid In a previous study [13], we showed that the LIM domains of LPP are the major units for targeting LPP to focal adhesions
We made use of a yeast two-hybrid system that is based on transcriptional activation of two reporter genes HIS3 and LacZ whose expression is driven by upstream GAL4 DNAbinding sites

Summary

Introduction

At sites of cell adhesion, proteins exist that perform structural tasks and have a signaling function. At the heart of structural and functional integrity of multicellular entities is the ability of each and every cell of it to successfully integrate signals arising from soluble factors, cell-substratum adhesion and cell-cell adhesion [1]. At sites of cell adhesion, more and more proteins are being identified that play a role in maintaining cell shape and motility but that, in addition to these structural functions, are implicated in signaling events. 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 (Fig. 1A). Because of its structural features and its characteristic to shuttle between the nucleus and the cytoplasm, LPP has been proposed to be a scaffolding protein involved in signal transduction from sites of cell adhesion to the nucleus

Methods

Results

Discussion

Conclusion