title: Ornithine decarboxylase antizyme Oaz3 modulates protein phosphatase activity.
abstract: Ornithine decarboxylase antizyme 3 (Oaz3) is expressed in spermatids, makes up the antizyme family of Oaz genes with Oaz1 and Oaz2, and was proposed to encode a 22 kDa antizyme protein involved in polyamine regulation similar to the 22 kDa OAZ1 and OAZ2 proteins. Here we demonstrate however that the major product encoded by Oaz3 is a 12 kDa protein, p12, which lacks the antizyme domain that interacts with ornithine decarboxylase. We show that p12 does not affect ornithine decarboxylase levels, providing an explanation for the surprising observation made in Oaz3 knock-out male mice, which do not display altered testis polyamine metabolism. This suggested a novel activity for Oaz3 p12. Using immuno-electron microscopy we localized p12 to two structures in the mammalian sperm tail, viz. the outer dense fibers and fibrous sheath, as well as to the connecting piece linking head and tail. We identified myosin phosphatase targeting subunit 3 (MYPT3), a regulator of protein phosphatase PP1β, as a major p12-interacting protein, and show that MYPT3 is present in sperm tails and that its ankyrin repeat binds p12. We show that MYPT3 can also bind protein phosphatase PP1γ2, the only protein phosphatase present in sperm tails, and that p12- MYPT3 interaction modulates the activity of both PP1β and PP1γ2. This is, to our knowledge, the first demonstration of a novel activity for an Oaz-encoded protein.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada and.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada and.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada and.
authors.forename: Young
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Anatomy & Cell Biology, Queens University, Kingston K7L 3N6, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Oko
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada and. Electronic address: fvdhoorn@ucalgary.ca.
authors.forename: Frans A
authors.initials: FA
authors.lastname: van der Hoorn
mesh_terms: D000818:Animals; D015317:Biogenic Polyamines / Q000096:biosynthesis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D013082:Sperm Tail / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
chemical_list: D015317:Biogenic Polyamines; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C512464:OAZ3 protein, human; C497526:Oaz3 protein, mouse; C517389:Oaz3 protein, rat; D065108:Ornithine Decarboxylase Inhibitors; C515115:PPP1R16A protein, human; D054645:Protein Phosphatase 1; D009955:Ornithine Decarboxylase