Control of Cellular Physiology by TM9 Proteins in Yeast and Dictyostelium

Abstract

TM9 proteins constitute a well defined family, characterized by the presence of a large variable extracellular domain and nine putative transmembrane domains. This family is highly conserved throughout evolution and comprises three members in Dictyostelium discoideum and Saccharomyces cerevisiae and four in humans and mice. In Dictyostelium, previous analysis demonstrated that TM9 proteins are implicated in cellular adhesion. In this study, we generated TM9 mutants in S. cerevisiae and analyzed their phenotype with particular attention to cellular adhesion. S. cerevisiae strains lacking any one of the three TM9 proteins were severely suppressed for adhesive growth and filamentous growth under conditions of nitrogen starvation. In these mutants, expression of the FLO11-lacZ reporter gene was strongly reduced, whereas expression of FRE(Ty1)-lacZ was not, suggesting that TM9 proteins are implicated at a late stage of nutrient-controlled signaling pathways. We also reexamined the phenotype of Dictyostelium TM9 mutant cells, focusing on nutrient-controlled cellular functions. Although the initiation of multicellular development and autophagy was unaltered in Dictyostelium TM9 mutants, nutrientcontrolled secretion of lysosomal enzymes was dysregulated in these cells. These results suggest that in both yeast and amoebae, TM9 proteins participate in the control of specific cellular functions in response to changing nutrient conditions.

The Golgi-Localized Arabidopsis Endomembrane Protein12 Contains Both Endoplasmic Reticulum Export and Golgi Retention Signals at Its C Terminus

“…Loss of Phg1A function in slime mold D. discoideum led to a defect in cellular adhesion and inefficient phagocytosis (Cornillon et al, 2000); similarly, Phg1b played a synergistic but not redundant role in controlling cellular adhesion and phagocytosis (Benghezal et al, 2003). EMPs in yeast were also found to be required for cell adhesion and filamentous growth under nitrogen starvation (Froquet et al, 2008). Interestingly, the human EMP protein, TM9SF4, was highly expressed in human malignant melanoma cells from metastatic lesions but was undetectable in healthy human tissues and cells, thus serving as a marker for malignancy (Lozupone et al, 2009).…”

“…Three EMP members are found in Dictyostelium discoideum (Phg1A to Phg1C) (Cornillon et al, 2000) and Saccharomyces cerevisiae (Tmn1 to Tmn3) (Froquet et al, 2008) and four members in human (TM9SF1 to TM9SF4) (Lozupone et al, 2009). Loss of Phg1A function in slime mold D. discoideum led to a defect in cellular adhesion and inefficient phagocytosis (Cornillon et al, 2000); similarly, Phg1b played a synergistic but not redundant role in controlling cellular adhesion and phagocytosis (Benghezal et al, 2003).…”

Dictyostelium EHD associates with Dynamin and participates in phagosome maturation

“…Glycosidase activity, phagosomal pH and proteolysis activity, and phagosomes purification Glycosidase activities in cell pellets and extracellular fluid were assessed as previously described (Froquet et al, 2008;Le Coadic et al, 2013). For phagosomal pH measurement, 3-µm carboxylated silica beads coupled to the pH-sensitive fluorophore FITC and to the pH-insensitive fluorophore Alexa-Fluor-594 were used.…”

TM9SF4 is required forDrosophilacellular immunity via cell adhesion and phagocytosis

“…TM9 proteins were found in endosomal or lysosomal fractions in yeast (Singer-Kruger et al, 1993), Dictyostelium (Benghezal et al, 2003) and human cells (Bagshaw et al, 2005;Diaz et al, 1997;Schimmoller et al, 1998) where they might participate in vesicular transport (Diaz et al, 1997). More recently, TM9 proteins were implicated in lysosomal secretion in Dictyostelium and cell signalling in both Dictyostelium and yeast (Froquet et al, 2008). However, no mutant or functional data are available at the level of a metazoan organism possessing a complex immune response.…”