Getting a GRASP on CASP: properties and role of the cytohesin-associated scaffolding protein in immunity

Abstract

Cytohesin-associated scaffolding protein (CASP) is a novel human adaptor protein that participates in the assembly and recruitment of protein complexes associated with intracellular trafficking and signaling. Owing to its exclusive expression in cells of hematopoietic origin, CASP has attracted attention from many groups of researchers as a potential key contributor to molecular mechanisms governing cells of the immune system. The functional characterization of CASP has involved a wide range of experimental approaches and provided broad and interesting insights that, collectively, distinguish CASP as an important contributor for a fully functioning and rapidly responsive immune system. Protein interaction studies have demonstrated that CASP interacts with members of the ADP ribosylation factor (ARF)-activating cytohesin family and with a unique PDZ domain-containing member of the sorting nexin family of endocytic trafficking proteins. Physiological knockout studies, however, have revealed that CASP may not be an essential protein in immunity under normal conditions, but rather a streamlining protein that greatly ameliorates the efficiency of the immune system under circumstances of significant stress. Interestingly, an evolutionarily related neuronal protein, called GRP1-associated scaffolding protein, may further participate in CASP-related functions in immune cells, conferring a level of redundancy in associated molecular pathways. In this review, we summarize and critically review the current literature, bringing together common themes from a variety of studies that, when considered together, provide new insights into the nature and significance of CASP function in the broad context of immunity.