Running title: CD157 mediates neutrophil adhesion and migration.

ABSTRACT CD157, a glycosylphosphatidylinositol(GPI)-anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that i) CD157 is a receptor, which induces reorganization of the cytoskeleton and significant changes in cell shape. ii) Signals mediated by CD157 act through modulation of cytosolic Ca 2+ concentration, and iii) are independent of the products of its enzymatic activities ( cyclic ADP-ribose and ADP i.e. -ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in DMSO-differentiated (CD157 + /CD38 - ) HL-60 cells, are hardly detectable. iv) The receptorial activity relies on cross-talk between CD157 and β 2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced