Synergistic Control of Cellular Adhesion by Transmembrane 9 Proteins

Abstract

The transmembrane 9 (TM9) family of proteins contains numerous members in eukaryotes. Although their function remains essentially unknown in higher eukaryotes, the Dictyostelium discoideum Phg1a TM9 protein was recently reported to be essential for cellular adhesion and phagocytosis. Herein, the function of Phg1a and of a new divergent member of the TM9 family called Phg1b was further investigated in D. discoideum. The phenotypes of PHG1a, PHG1b, and PHG1a/PHG1b double knockout cells revealed that Phg1a and Phg1b proteins play a synergistic but not redundant role in cellular adhesion, phagocytosis, growth, and development. Complementation analysis supports a synergistic regulatory function rather than a receptor role for Phg1a and Phg1b proteins. Together, these results suggest that Phg1 proteins act as regulators of cellular adhesion, possibly by controlling the intracellular transport in the endocytic pathway and the composition of the cell surface.

Dictyostelium discoideum Developmentally Regulated Genes Whose Expression Is Dependent on MADS Box Transcription Factor SrfA

“…D. discoideum proteins of the TM9 family have been described recently, and a direct sequence comparison has shown that sigC codes for the Phg1b protein (5).…”

“…phg1b codes for a protein with nine predicted transmembrane regions, homologous to the TM9 family of endoplasmic proteins. Mutation of this gene causes temperature-dependent defects in cell adhesion and phagocytosis (5). The SrfA-dependent alternatively spliced mRNA codes for an internally deleted protein that lacks part of the predicted first extracytoplasmic domain and the first transmembrane fragment.…”

Glycoprotein gp130 ofDictyostelium discoideumInfluences Macropinocytosis and Adhesion

“…Cell-cell recognition and adhesion are vital aspects of this developmental progression, and researchers have established that cell-surface molecules, including gp24 (Knecht et al, 1987;Loomis, 1988;Brar and Siu, 1993), gp80 (Muller and Gerisch, 1978;Noegel et al, 1986), and gp150 (Gao et al, 1992;Wang et al, 2000), are mediating these interactions (reviewed in Kessin, 2001 andSiu et al, 2004). An understanding of the plasma membrane molecules involved in adhesive events during phagocytosis and motility of vegetative amoebae is emerging with the recent identification of cell-substrate adhesion molecule, sadA (Fey et al, 2002) and the phg1 family of transmembrane 9 proteins (Cornillon et al, 2000;Benghezal et al, 2003).In this study, we present evidence that a plasma membrane glycoprotein gp130 also played a role in cell-substrate adhesion during vegetative growth. Postulated to be a phagocytosis receptor (Chia, 1996), gp130 is possibly the same molecule as gp126, a surface-exposed glycoprotein suggested to have a dual role as both a phagocytosis receptor and a mediator of cell-cell cohesion (Chadwick and Garrod, 1983;Chadwick et al, 1984;Chadwick, 1986).…”

“…Phagocytosis by the gp130-null cells could be performed by the "nonspecific" receptors that compensated for gp130 so its absence was not a liability. We also consider the possibility that gp130 was part of the cellular adhesion assemblage of surface molecules postulated to be controlled by the transmembrane 9 family of proteins Benghezal et al (2003). Thus, gp130 could still have a role in phagocytosis as a specific receptor.…”

“…Cell-cell recognition and adhesion are vital aspects of this developmental progression, and researchers have established that cell-surface molecules, including gp24 (Knecht et al, 1987;Loomis, 1988;Brar and Siu, 1993), gp80 (Muller and Gerisch, 1978;Noegel et al, 1986), and gp150 (Gao et al, 1992;Wang et al, 2000), are mediating these interactions (reviewed in Kessin, 2001 andSiu et al, 2004). An understanding of the plasma membrane molecules involved in adhesive events during phagocytosis and motility of vegetative amoebae is emerging with the recent identification of cell-substrate adhesion molecule, sadA (Fey et al, 2002) and the phg1 family of transmembrane 9 proteins (Cornillon et al, 2000;Benghezal et al, 2003).…”