Innate immunity is constructed around genetically encoded receptors that survey the intracellular and extracellular environments for signs of invading microorganisms. These receptors recognise the invader and through complex intracellular networks of molecular signaling, they destroy the threat whilst instructing effective adaptive immune responses. Many of these receptors, like the Toll-like receptors in particular, are well-known for their ability to mediate downstream responses upon recognition of exogenous or endogenous ligands; however, the emerging family known as the C-type lectin-like receptors contains many members that have a huge impact on immune and homeostatic regulation. Of particular interest here are the C-type lectin-like receptors that make up the Dectin-1 cluster and their intracellular signaling motifs that mediate their functions. In this review, we aim to draw together current knowledge of ligands, motifs and signaling pathways, present downstream of Dectin-1 cluster receptors, and discuss how these dictate their role within biological systems.

CLEC-1 is almost completely uncharacterised and although there is evidence to suggest a few conserved residues between the mouse and humans, none of these have been proven to aid in downstream signaling to date. Bioinformatic predictions into the structure of CLEC-1 describe it as being a group V type II transmembrane receptor with some potentially noteworthy residues present within its intracellular tail [66, 87]. Literature also describes two conserved cysteine residues within the stalk region that are hypothesised to allow CLEC-1 to form homodimers facilitated by disulphide bridges [88]. However, functional work on CLEC-1 is restricted due to the lack of a known ligand. Notable residues within the intracellular tail are a tyrosine that presents itself in an undefined signaling sequence [YSST] as well as the presence of a tri-acidic cluster [DDD] that could potentially mediate signaling in ways analogous to tyrosine-independent signaling instigated by Dectin-1 [66, 87] (Figure 5). However there are no data to support either of these being a functional motif.