title: Nodal stability determines signaling range.
abstract: Secreted TGFbeta proteins of the Nodal family pattern the vertebrate body axes and induce mesoderm and endoderm . Nodal proteins can act as morphogens , but the mechanisms regulating their activity and signaling range are poorly understood. In particular, it has been unclear how inefficient processing or rapid turnover of the Nodal protein influences autocrine and paracrine signaling properties . Here, we evaluate the role of Nodal processing and stability in tissue culture and zebrafish embryos. Removal of the pro domain potentiates autocrine signaling but reduces Nodal stability and signaling range. Insertion of an N-glycosylation site present in several related TGFbeta proteins increases the stability of mature Nodal. The stabilized form of Nodal acts at a longer range than the wild-type form. These results suggest that increased proteolytic maturation of Nodal potentiates autocrine signaling, whereas increased Nodal stability extends paracrine signaling.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
authors.forename: J Ann
authors.initials: JA
authors.lastname: Le Good
authors.forename: Katherine
authors.initials: K
authors.lastname: Joubin
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Giraldez
authors.forename: Nadav
authors.initials: N
authors.lastname: Ben-Haim
authors.forename: Séverine
authors.initials: S
authors.lastname: Beck
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Constam
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D016296:Mutagenesis; D055457:Nodal Protein; D019899:Paracrine Communication / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D017931:DNA Primers; C526007:NODAL protein, human; D055457:Nodal Protein; D016212:Transforming Growth Factor beta