Structural characterization and subcellular localization of Drosophila organic solute carrier partner 1

Abstract

BackgroundOrganic solute carrier partner 1 (OSCP1) is known to facilitate the transport of various organic solutes into cells and reported to play a role in cell growth and cell differentiation. Moreover, OSCP1 is known as a tumor suppressor gene that is frequently down-expressed in nasopharyngeal carcinomas and acute myeloid leukemia. However, the underlying mechanisms of action remain unclear and the subcellular localization of OSCP1 has yet to be determined in detail.ResultsDrosophila contains a single orthologue of OSCP1 (dOSCP1) that shares 58% homology with its human counterpart. To study the expression pattern and subcellular localization of dOSCP1, we prepared a specific antibody. Subcellular localization analyses of dOSCP1 with these revealed localization in the plasma membrane, endoplasmic reticulum, Golgi apparatus and mitochondria, but no detection in cytosol. dOSCP1 signals were also detected in the nucleus, although at weaker intensity than in plasma membranes and subcellular organelles. In addition, native polyacrylamide gel electrophoresis analysis with and without β-mercaptoethanol treatment revealed that recombinant dOSCP1 forms dimers and trimers in solution. The dimer form of dOSCP1 could also be detected by Western immunoblot analyses in third instar larval extracts.ConclusionsThe data revealed that dOSCP1 localizes not only in the plasma membrane but also in the nucleus, ER, Golgi apparatus and mitochondria. It is therefore conceivable that this protein may interact with various partners or form multimeric complexes with other proteins to play multiple roles in cells, providing clues to understanding the functions of dOSCP1 during Drosophila development.

The NOR1/OSCP1 proteins in cancer: from epigenetic silencing to functional characterization of a novel tumor suppressor

“…Huu NT et al. found that dNOR1/dOSCP1 localizes in endoplasmic reticulum (ER) in salivary gland cells31. Interestingly, overexpression of dNOR1/dOSCP1 caused ER stress in Drosophila salivary gland cells, as evidenced by increase of ER chaperones marker KDEL immunostaining 26.…”

“…At present, except for human NOR1 gene, mouse, rat and Drosophila orthologue of NOR1 was successively isolated and well characterized29-31 (Figure 1A) (Table 1). Among these orthologues, mouse NOR1 (mNOR1) and Drosophila NOR1 (dNOR1) share 86% and 58% homology with its human counterpart, respectively 17, 31. Human NOR1/OSCP1 gene consists of 11 exons which is mapped to chromosome 1p34.2 and spans 33.4 kb of the genomic DNA.…”

“…However, Drosophila orthologue of OSCP1 (dOSCP1) exhibits a more ubiquitous tissue distribution pattern including brain lobes, leg discs, wing discs, eye discs, fat bodies and salivary glands31. Thus, the tissue expression pattern of NOR1 orthologues seems to be different across multiple species.…”

“…However, it was also found to distribute in pre- and post-synaptic compartments, but not associated with synaptic membranes or mitochondria 34. Surprisingly, it has been shown that dOSCP1 distributes not only in ER, Golgi apparatus and mitochondria, but also to the plasma membrane and even translocate into the nucleus 31. Thus, the subcellular location of NOR1/OSCP1 protein may be variable among species and different cell types (Table 1).…”

Tumor suppressor gene OSCP1/NOR1 regulates apoptosis, proliferation, differentiation, and ROS generation during eye development of Drosophila melanogaster

“…Although possible roles of OSCP1 have been reported using mammalian cell lines, only limited information is available regarding the function of OSCP1 in living organisms. In previous studies, we reported that Drosophila contains a single ortholog of OSCP1/NOR1 named dOSCP1 (CG13178) that shares 58% homology with its human counterpart . In the present study, we utilized the Drosophila melanogaster model for functional analysis of dOSCP1.…”