Role of Lgl/Dlg/Scribble in the regulation of epithelial junction, polarity and growth
Tomoyuki Yamanaka1,2 Shigeo Ohno2
1
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan, 2Department of Molecular Biology, Yokohama City University, Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Lgl/Dlg/Scribble in Drosophila
- 3.1. Identification of the tumor suppressors Lgl, Dlg and Scribble, and their roles in the establishment of epithelial cell polarity and junctions in Drosophila
- 3.2. Antagonistic interactions between laterally localized Lgl/Dlg/Scribble and apical polarity proteins
- 3.3. Molecular mechanism of the regulation of epithelial cell junctions, polarity and proliferation by Lgl
- 3.4. Molecular mechanism of the regulation of epithelial cell junctions, polarity and proliferation by Dlg and Scribble
- 4. Lgl/Dlg/Scribble in C. elegans
- 4.1. Essential roles of Dlg1 and Let-413 in the establishment of AJs in C. elegans
- 5. Lgl/Dlg/Scribble in vertebrates
- 5.1. Molecular mechanism and functional significance of antagonistic interaction between Lgl1/2 and apical polarity proteins in vertebrate epithelial cells
- 5.2. Functional analysis of hDlg1/SAP97 and Scrb1 in mammalian epithelial cells
- 5.3. Molecular interactions of Lgl1/2, Scrb1 and hDlg1/SAP97 at lateral region of vertebrate epithelial cells
- 5.4. Possible roles of Lgl1/2, hDlg1/SAP97 and Scrb1 in epithelial tumorigenesis in mammals
- 6. Summary and Perspectives
- 7. Acknowledgement
- 8. References
1. ABSTRACT
Genetic studies in Drosophila have revealed that three tumor suppressors, Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl), which localize to the basolateral region of epithelial cells, cooperatively regulate cell polarity, junction formation and cell growth in epithelial cells. Subsequent studies in Drosophila, vertebrates and C. elegans have shown the evolutionary conservation of some of their functions in epithelial cells. Also, these studies revealed the importance of antagonistic interactions between these tumor suppressors and apical polarity regulators such as Crumbs and aPKC for the establishment of apical-basal polarity with organized cell-cell junctions and regulation of cell growth in epithelial cells.
