CLEC receptors, endocytosis and calcium signaling

Abstract

Proper immune system function is dependent on precisely evolved sensing and signal transduction events that occur at cellular and subcellular compartment boundaries. Recent immunotherapeutic efforts have generally focused on the roles that two specific protein superfamilies play in such events. This review is directed at a third superfamily, the C-type (Ca2+-dependent) lectin-type (CLEC) receptors and the nuanced, less traditionally acknowledged, yet quite important, role of endocytic-based calcium signaling. While extracellular recognition events rely heavily on the sophisticated structural diversity that lectins and glycobiology have to offer, the actual details of CLEC receptor-mediated, endocytic-based, calcium signal transduction have remained less appreciated. Because many CLEC receptor family members are emerging, not only as biomarkers for critical immune cell subpopulations, but also proving to be selective and pivotal modulators of immune function, this review seeks to promote the potential role CLEC receptor-initiated calcium signaling plays in immunotherapy. Given the importance of calcium signaling, these receptors provide a means to initiate a selective physiological response.

Keywords

• C-Type lectin-type receptors
• endocytosis
• endosomal pathways
• antigen processing
• calcium signaling
• mannose receptor family
• DC-SIGN (CD209)
• CLEC10A (CD301)