The Nonaspanins TM9SF2 and TM9SF4 Regulate the Plasma Membrane Localization and Signalling Activity of the Peptidoglycan Recognition Protein PGRP-LC in <b><i>Drosophila</i></b>

Abstract

Transmembrane 9 (TM9) proteins, or nonaspanins, are a family of proteins conserved throughout evolution and characterized by 9 transmembrane domains. In Drosophila, TM9 superfamily protein member 4 (TM9SF4) and its closest paralogue, TM9SF2, contribute to phagocytosis of various types of particles, while TM9SF4 displays non-redundant requirement in Gram-negative bacteria engulfment. In addition, the two TM9 proteins control the actin cytoskeleton in larval haemocytes and in Drosophila S2 cells. Here, we show that TM9SF4 and TM9SF2 co-immunoprecipitate with the peptidoglycan recognition protein (PGRP)-LC, which triggers the Drosophila immune response to bacterial infection. Furthermore, both TM9 proteins co-localize with this receptor in intracellular vesicles and at the plasma membrane in Drosophila S2 cells in culture and in the fly fat body. Silencing TM9SF4 prevents plasma membrane localization of PGRP-LC, whereas silencing TM9SF2 does not, which may account for the non-redundant role of TM9SF4 in phagocytosis of Gram-negative bacteria. Finally, we provide a set of data suggesting that TM9 proteins can prevent inappropriate signalling from the unstimulated receptor.

TM9SF4 is a novel V-ATPase-interacting protein that modulates tumor pH alterations associated with drug resistance and invasiveness of colon cancer cells

“…Conversely, in TM9SF4-KD cells this colocalization was completely lost (Figure 1c), confirming the specificity of the staining. Consistent with our previous results and with the literature on ATP6V0A2, 10,18 no colocalization of TM9SF4 and LAMP1 was observed (Figure 1d). Effective TM9SF4 silencing was verified by quantitative PCR (Supplementary Figure S1A).…”

“…[14][15][16][17] TM9SF4 is a transmembrane protein belonging to the transmembrane-9 superfamily (TM9SF), which is a well-defined family of proteins characterized by a large hydrophilic N-terminal domain followed by nine transmembrane domains. 18 Although little is known about their function, these proteins have been implicated in adhesion, phagocytosis and innate immunity. Recently, TM9SF1 has been identified as an autophagy-regulating protein 19 and reported to be differentially expressed in urinary bladder cancer cells, 20 while the TM9SF3 gene has been shown to be upregulated in paclitaxel-resistant breast cancer cell lines and its overexpression has been related with poor gastric cancer patients outcome.…”

The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

“…The scavenger receptor dSR-CI and a transmembrane protein, Eater, bind to both Gram-negative and -positive bacteria [26,27]. The membrane receptor PGRP-LC binds to and engulfs Gram-negative but not Gram-positive bacteria, and its membrane localization is dependent on the nonaspanin TM9SF4 [28,29]. Draper (Drpr) promotes clearance and degradation of neuronal debris and apoptotic cells via phagosome maturation, as well as phagocytosis of Staphylococcus aureus (S .…”

Transcriptome Characterization of the Chinese Fir (Cunninghamia lanceolata (Lamb.) Hook.) and Expression Analysis of Candidate Phosphate Transporter Genes

“…The AAA gene family has been reported as an obligate exchange translocase specific for ATP and ADP, and can also transport inorganic phosphate [59]. Unigene c258053-g1 was annotated to the transmembrane 9 superfamily member 2 (TM9SF2), which encodes a member of the transmembrane 9 superfamily and plays a role in small molecule transport or acts as an ion channel [60]. In total, there are 45 candidate PHT unigenes expressed in root tissue, and 12 unigenes expressed in leaves and stem tissue.…”