title: Evidence for the interaction of D-amino acid oxidase with pLG72 in a glial cell line.
abstract: Accumulating genetic evidence indicates that the primate-specific gene locus G72/G30 is related to schizophrenia: it encodes for the protein pLG72, whose function is still the subject of controversy. We recently demonstrated that pLG72 negatively affects the activity of human d-amino acid oxidase (hDAAO, also related to schizophrenia susceptibility), which in neurons and (predominantly) in glia is expected to catabolize the neuromodulator d-serine. The d-serine regulation mechanism relying on hDAAO-pLG72 interaction does not match with the subcellular localizations proposed for hDAAO (peroxisomes) and pLG72 (mitochondria). By using glioblastoma U87 cells transfected with plasmids encoding for hDAAO and/or pLG72 we provide convergent lines of evidence that newly synthesized hDAAO, transitorily present in cytosol before being delivered to the peroxisomes, colocalizes and interacts with pLG72 which we propose to be exposed on the external membrane of mitochondria. We also report that newly synthesized cytosolic hDAAO is catalytically active, and therefore pLG72 binding-and ensuing hDAAO inactivation-plays a protective role against d-serine depletion.
authors.affiliation: Dipartimento di Biotecnologie e Scienze Molecolari, Università degli studi dell'Insubria, via JH Dunant 3, 21100 Varese, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sacchi
authors.forename: Pamela
authors.initials: P
authors.lastname: Cappelletti
authors.forename: Stefano
authors.initials: S
authors.lastname: Giovannardi
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation / Q000379:methods; D002460:Cell Line; D003605:D-Amino-Acid Oxidase / Q000235:genetics / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D003605:D-Amino-Acid Oxidase