Nodal Stability Determines Signaling Range

Autor: Nadav Ben-Haim, Séverine Beck, Antonio J. Giraldez, Daniel B. Constam, Yu Chen, Katherine Joubin, Alexander F. Schier, J. Ann Le Good
Jazyk: angličtina
Předmět:
Mesoderm
animal structures
Nodal Protein
Immunoblotting
Molecular Sequence Data
Gene Expression
Nodal signaling
Biology
Transfection
General Biochemistry
Genetics and Molecular Biology

Cell Line
03 medical and health sciences
Paracrine signalling
Tissue culture
0302 clinical medicine
Transforming Growth Factor beta
Chlorocebus aethiops
Paracrine Communication
medicine
Animals
Humans
Amino Acid Sequence
Autocrine signalling
Zebrafish
Body Patterning
DNA Primers
030304 developmental biology
0303 health sciences
Agricultural and Biological Sciences(all)
Biochemistry
Genetics and Molecular Biology(all)

Lefty
Sequence Analysis
DNA

Protein Structure
Tertiary

Cell biology
Autocrine Communication
medicine.anatomical_structure
Mutagenesis
COS Cells
Endoderm
General Agricultural and Biological Sciences
NODAL
Sequence Alignment
030217 neurology & neurosurgery
Signal Transduction
Zdroj: Current Biology. (1):31-36
ISSN: 0960-9822
DOI: 10.1016/j.cub.2004.12.062
Popis: Secreted TGFβ proteins of the Nodal family pattern the vertebrate body axes and induce mesoderm and endoderm [1]. Nodal proteins can act as morphogens [2], 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 [3, 4]. 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 TGFβ 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.
Databáze: OpenAIRE