The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

Abstract

Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature. J. Leukoc. Biol. 65: 151-161; 1999.

Human Anti-CD38 Autoantibodies Raise Intracellular Calcium and Stimulate Insulin Release in Human Pancreatic Islets

“…To our knowledge, these results provide the first evidence that autoantibodies with agonist properties on the CD38 effector system-i.e., [Ca 2ϩ ] i -occur in nature. These findings also support the receptor nature of the CD38 molecule and its ability to activate outside/inside signaling (20). Furthermore, they indirectly confirm the existence of one or more ligands (14), whose interaction with functional domains of the CD38 molecule is mimicked by the natural autoantibodies.…”

NAD+ and ATP Released from Injured Cells Induce P2X7-Dependent Shedding of CD62L and Externalization of Phosphatidylserine by Murine T Cells

“…The type II transmembrane protein CD38 is a potent ecto-NADglycohydrolase (ecto-NADase) (19,20) expressed by lymphocytes, endothelial cells, and several other cell types. CD38-deficient mice show impaired humoral immune responses, neutrophil chemotaxis, and dendritic cell (DC) trafficking (21)(22)(23).…”

Hyaluronan-binding Proteins: Tying Up the Giant

“…This protein is an enzyme with NADase activity, and this property has been studied much more extensively than its hyaluronan binding function for which no biological role has yet been ascribed (24).…”