Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice

Pantetheinase (EC 3.5.1.-) is an ubiquitous enzyme which in vitro has been shown to recycle pantothenic acid (vitamin B5) and to produce cysteamine, a potent anti-oxidant, We show that the Vanin-1 gene encodes pantetheinase w idely expressed in mouse tissues: (1) a pantetheinase activity is specifica lly expressed by Vanin-1 transfectants and is immunodepleted by specific an tibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantethei nase activity in kidney and liver; (4) in these organs, a major metabolic c onsequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissu es under physiological conditions. Since the Vanin-1 molecule was previousl y shown to be involved in the control of thymus reconstitution following su blethal irradiation in vivo, this raises the possibility that Vanin/panteth einase might be involved in the regulation of some immune functions maybe i n the context of the response to oxidative stress. (C) 2000 Federation of E uropean Biochemical Societies. Published by Elsevier Science B.V. All right s reserved.