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 widely expressed in mouse tissues: (1) a pantetheinase activity is specifically expressed by Vanin-1 transfectants and is immunodepleted by specific antibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantetheinase activity in kidney and liver; (4) in these organs, a major metabolic consequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. Since the Vanin-1 molecule was previously shown to be involved in the control of thymus reconstitution following sublethal irradiation in vivo, this raises the possibility that Vanin/pantetheinase might be involved in the regulation of some immune functions maybe in the context of the response to oxidative stress.
Pitari
G
G
Dipartmento di Biologia di Base ed Applicata Università di L'Aquila, Italy.
Malergue
F
F
Martin
F
F
Philippe
J M
JM
Massucci
M T
MT
Chabret
C
C
Maras
B
B
Duprè
S
S
Naquet
P
P
Galland
F
F
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003543:Cysteamine / Q000378:metabolism; D058851:GPI-Linked Proteins; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D017403:In Situ Hybridization; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010802:Phylogeny; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D003543:Cysteamine; D000581:Amidohydrolases; C022314:pantetheinase