[Frontiers in Bioscience 14, 2149-2169, January 1, 2009]

Crumbs proteins in epithelial morphogenesis

Elsa Bazellieres, Emeline Assemat, Jean-Pierre Arsanto, Andre Le Bivic, Dominique Massey-Harroche

Institut de Biologie du Developpement de Marseille-Luminy, CNRS UMR 6216 et Universite de la Mediterranee, Parc Scientifique et Technologique de Luminy, Case 907, 13288 Marseille Cedex 09, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3.Crumbs proteins: evolution and scaffolding
3.1.Evolution of Crumbs proteins among known animal genomes
3.2.Scaffolding of Crumbs complex in Drosophila melanogaster and mammals
3.2.1.Crumbs complex in Drosophila melanogaster
3.2.1.1. Partners of DCrumbs
3.2.1.2. Partners of Stardust
3.2.1.3. Partners of DPatj
3.2.2.Crumbs complex in mammals
3.2.2.1. Partners of CRB3
3.2.2.2. Partners of PALS1
3.2.2.3.Partners of PATJ
4.Crumbs complex: role in developing organisms
4.1.Early embryogenesis and primary epithelia
4.1.1. Drosophila melanogaster
4.1.2. Vertebrates
4.2.Organogenesis
4.2.1.Retina
4.2.1.1. Drosophila retina
4.2.1.2. Zebrafish retina
4.2.1.3. Mammalian retina
4.2.2.Kidney
4.2.2.1. Zebrafish kidney
4.2.2.2. Mammalian kidney
5.Crumbs complex: role in epithelial cell cultures
5.1.Cell cultures: a model system for studying the function of CRB3A complex
5.2.Genetic approaches
5.2.1. CRB3 knockdown and overexpressing cells
5.2.2. PALS1 knockdown cells
5.2.3. PATJ knockdown cells
5.3.CRB3 induces de novo tight junction formation
6.Perspective on CRB function
6.1.CRB3A is linked to actin-binding proteins
6.2.CRB3A and trafficking
6.3.CRB complexes and cell proliferation
7. Acknowlegments
8.References

1. ABSTRACT

Cell polarity is an essential feature of most eukaryotic cells, especially epithelial cells in multicellular animals. Polarity protein complexes that regulate epithelial organization have been identified. In this review, it is proposed to describe how the Crumbs complex acts in the process of cell polarity and epithelial organization. During the last decade, several partners of Crumbs, an apical transmembrane protein, have been identified and their direct or indirect associations with the cytoplasmic domain of Crumbs have been dissected. In addition, mutants of several of the genes encoding proteins belonging to the Crumbs network have been obtained in animals ranging from flies to mouse, which have led to a better understanding of their functions in vivo. These functions include polarity axis formation, stabilization of epithelial apico-lateral junctions, photoreceptor organization and ciliogenesis. Since human CRUMBS1 mutations are associated with retina degeneration, it has become essential to define Crumbs network and to understand exactly how this network acts in polarized cells, with a view to developing suitable therapeutic approaches for treating this severe degenerative disease.