Low density lipoprotein receptors LRP-1 and LRP-2 in C. elegans

Abstract

The regulation of vulval cell lineage polarity is controlled by Wnt signaling. Previously known components involved in the regulation of vulval cell lineage polarity include LIN-17, LIN-18, CAM-1, and VANG-1 (Inoue et al., 2004; Gleason et al., 2006; Green et al., 2008). A directed bioinformatics screen of known Wnt pathway components was performed to find additional genes involved in directing vulval orientation. A BLAST was run using other known Wnt receptors and it was determined that C. elegans does not contain a true ortholog of Drosophila LRP5/6 (Arrow) (He et al., 2004; Eisenmann, 2005), but does have multiple low-density lipoprotein receptors, including LRP-1 and LRP-2 (Figure 1). Like other low-density lipoprotein receptors, both LRP-1 and LRP-2 contain many LDLR Domain Class A and Class B repeats, EGF-like domains, and a transmembrane domain. However, having approximately three times as many amino acids, LRP-1 and LRP-2 are more similar to megalin than LRP5/6 (Yochem et al., 1999). The absence of LRP5/6 within C. elegans but presence in flies and all other higher order organisms suggests that the gene encoding LRP5/6 arose after nematodes, potentially from either LRP1 or LRP2/megalin, as both receptors contain the entire extracellular portion of LRP5/6 in a single contiguous sequence block (Figure 1). Our examination of the protein sequence of LRP-1 and LRP-2 indicates that most nematodes have at least two copies of LRP-like proteins with C. elegans LRP-1 and LRP-2 being highly similar possibly due to a recent duplication and divergence (Figure 2). Comparing the sequences across Caenorhabditis we find that LRP-1 proteins cluster together and LRP-2 proteins also form their own cluster. Based on location in the genome and sequence similarity from protein alignment, we believe that Caenorhabditis lrp-2 is a recent duplication and divergence of lrp-1 (Figure 2).

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