Nuclear pore membrane glycoprotein 210 as a new marker for epithelial cells

University dissertation from Uppsala : Acta Universitatis Upsaliensis

Abstract: Epithelial cell polarisation is a prerequisite for the branching morphogenesis in several organs. Differential screening techniques were used to identify genes, which are upregulated during induction of epithelium in early kidney development. This investigation revealed two separate genes, Nuclear localising protein 1 (Nulp1), a previously undescribed gene with sequence characteristics of the basic helix-loop-helix transcription factor family, and glycoprotein 210 (gp210, POM210), an integral membrane protein constituent of the nuclear pore complex (NPC). Of these, gp210 was found to be upreglated during conversion of mesenchyme to epithelium. The nuclear envelope, which demarcates the nuclear region in the eukaryotic cell, consists of an inner and an outer membrane that are fused at the locations for NPCs. These large macromolecular assemblages are tube like structures connecting the cytoplasmic and nuclear compartments of the cell. NPCs serve as the only conduits for exchange of molecular information between these cellular rooms. Electron microscopy techniques have revealed detailed information about the NPC architecture. A number of proteins (nucleoporins) have been characterised and embodied as components of the NPC structure. Active, energy dependent nucleocytoplasmic transport of RNAs and proteins is mediated by a group of soluble receptor proteins, collectively termed karyopherins. Gp210 has been suggested to be important for nuclear pore formation. Nevertheless, our analyses showed a limited expression pattern of gp210, with its mRNA and protein largely confined to epithelial cells in the mouse embryo. Furthermore, in several cell lines, gp210 was undetectable. The expression pattern of gp210 was not synchronised with some other nucleoporins, indicating NPC heterogeneity. Characterisation of the structure of the human gp210 gene, including its promoter region, gave insight about possible cell-type specific gene regulatory mechanisms. Regulation of molecular traffic between the nucleus and the cytoplasm leads to transcriptional control. Cell specific configuration of the NPC structure, due to diffential expression of gp210, could be involved in this control. Gp210 could be of importance for the development of epithelial cell polarisation.