Niemann-Pick C2 Proteins: A New Function for an Old Family

Abstract

Niemann-Pick proteins type C2 (NPC2) are carriers of cholesterol in vertebrates, with a single member in each species. The high sequence conservation between mammals and across vertebrates is related to their common function. In contrast, NPC2 proteins in arthropods have undergone extensive duplication and differentiation, probably under environmental pressure, and are likely to have different functions. Recent studies have suggested that in arthropods these proteins might act as carriers for semiochemicals and other hydrophobic compounds. In this study we focused on the function of a specific NPC2 gene in the moth Helicoverpa armigera (HarmNPC2-1). This protein binds several flavonoids with micromolar dissociation constants. The best ligand was gossypol, present in cotton, one of the main host plants for H. armigera. Western blot revealed the presence of HarmNPC2-1 in different parts of the body, including the antennae, proboscis, and abdomen. In the antennae, in situ hybridization experiments produced strong staining in auxiliary cells at the base of sensilla trichodea, basiconica, coeloconica, and chaetica. Immunocytochemistry confirmed the expression of the protein in sensilla chaetica. Our results support a role of semiochemical carriers for NPC2 proteins in insects and indicate such proteins as new targets for insecticide-free pest population control.

Comparative morphological and transcriptomic analyses reveal novel chemosensory genes in the poultry red mite,Dermanyssus gallinaeand knockdown by RNA interference

“…This study found that NPC2 was expressed not only in chemosensory sensilla, but also in other parts of the body, suggesting roles in both chemical detection as well as in other functions. The results of this study were consistent with other studies in arthropods, which showed wide expression of NPC2 proteins across the body (Ishida et al, 2014; Pelosi et al, 2017; Zhu et al, 2018).…”

Proteomic analysis of chemosensory organs in the honey bee parasite Varroa destructor: A comprehensive examination of the potential carriers for semiochemicals

“…XP_001844693), indicating a result of contamination. Furthermore, the two CSPs reported in a transcriptome study of the mite Tyrophagus putrescentiae 29 A third family of proteins possibly acting as semiochemical carriers in insects include the NPC2 (Niemann-Pick proteins of type C2) proteins [30][31][32] . This family is well represented in Chelicerata with a variable number of genes 31,33 , depending on the species.…”

“…Members of the NPC2 family have been also found in the tick Amblyomma americanum 35 and eight transcripts encoding such proteins have recently been reported in a transcriptome project in Varroa chemosensory organs 26 . For NPC2 proteins, a function of semiochemical carriers seems to be well supported by their ligand-binding properties as well as by their localization in chemosensilla 30,32,34 . Moreover, three-dimensional structures of NPC2 members both from vertebrates and insects are available, some of them containing hydrophobic ligands inside their binding pockets 30,36 .…”

Varroa chemosensory proteins: some are conserved across Arthropoda but others are arachnid specific

“…The role of NPC2s as semiochemical carriers, and not just as lipid carriers, is a relatively new concept that emerged from the discovery of CjapNPC2, which binds to several semiochemicals in the basiconica sensilla on the antennae of the ant Camponotus japonicus (Ishida et al, 2014). This discovery led to the finding of NPC2 homologues in other arthropods, but only a few NPC2s were suggested to play a role as semiochemicals carriers, also in insects (Zhu et al, 2018). We searched the Varroa transcriptome for possible CjapNPC2 homologues using a local BLASTp search (accession ID: BAO48214) and found that TRINITY_DN80297_c0_g1_i1, one of the six Varroa NPC2 members, had the highest similarity across the entire Varroa transcriptome (e-value = 3 E-17), suggesting that this transcript is a Varroa CjapNPC2 homologue.…”