title: Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking.
abstract: Antizyme inhibitor 1 (AZIN1) and 2 (AZIN2) are proteins that activate ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis. Both AZINs release ODC from its inactive complex with antizyme (AZ), leading to formation of the catalytically active ODC. The ubiquitously expressed AZIN1 is involved in cell proliferation and transformation whereas the role of the recently found AZIN2 in cellular functions is unknown. Here we report the intracellular localization of AZIN2 and present novel evidence indicating that it acts as a regulator of vesicle trafficking. We used immunostaining to demonstrate that both endogenous and FLAG-tagged AZIN2 localize to post-Golgi vesicles of the secretory pathway. Immuno-electron microscopy revealed that the vesicles associate mainly with the trans-Golgi network (TGN). RNAi-mediated knockdown of AZIN2 or depletion of cellular polyamines caused selective fragmentation of the TGN and retarded the exocytotic release of vesicular stomatitis virus glycoprotein. Exogenous addition of polyamines normalized the morphological changes and reversed the inhibition of protein secretion. Our findings demonstrate that AZIN2 regulates the transport of secretory vesicles by locally activating ODC and polyamine biosynthesis.
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Kanerva
authors.forename: Laura T
authors.initials: LT
authors.lastname: Mäkitie
authors.forename: Nils
authors.initials: N
authors.lastname: Bäck
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002262:Carboxy-Lyases; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002460:Cell Line; D006801:Humans; D051379:Mice; D016253:Microscopy, Immunoelectron; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D034622:RNA Interference; D022142:Secretory Vesicles / Q000378:metabolism / Q000648:ultrastructure; D021601:trans-Golgi Network / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; D011073:Polyamines; C039317:ornithine decarboxylase antizyme inhibitor; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; C546395:AZIN2 protein, human