title: XPACE4 is a localized pro-protein convertase required for mesoderm induction and the cleavage of specific TGFbeta proteins in Xenopus development.
abstract: XPACE4 is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the TGFbeta family of signaling molecules. Studies in mouse suggest it may have important roles in regulating embryonic tissue specification. Here, we examine the role of XPACE4 in Xenopus development and make three novel observations: first, XPACE4 is stored as maternal mRNA localized to the mitochondrial cloud and vegetal hemisphere of the oocyte; second, it is required for the endogenous mesoderm inducing activity of vegetal cells before gastrulation; and third, it has substrate-specific activity, cleaving Xnr1, Xnr2, Xnr3 and Vg1, but not Xnr5, Derriere or ActivinB pro-proteins. We conclude that maternal XPACE4 plays an important role in embryonic patterning by regulating the production of a subset of active mature TGFbeta proteins in specific sites.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Bilge
authors.initials: B
authors.lastname: Birsoy
authors.forename: Linnea
authors.initials: L
authors.lastname: Berg
authors.forename: P Huw
authors.initials: PH
authors.lastname: Williams
authors.forename: James C
authors.initials: JC
authors.lastname: Smith
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Wylie
authors.forename: Jan L
authors.initials: JL
authors.lastname: Christian
authors.forename: Janet
authors.initials: J
authors.lastname: Heasman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D008969:Molecular Sequence Data; D009035:Mothers; D016376:Oligonucleotides, Antisense / Q000235:genetics; D019899:Paracrine Communication; D010641:Phenotype; D043484:Proprotein Convertases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C513085:PCSK6 protein, Xenopus; C080654:PCSK6 protein, human; C513086:Pcsk6 protein, mouse; D043484:Proprotein Convertases; D012697:Serine Endopeptidases