Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans

Development. 1999 Jan;126(2):251-60. doi: 10.1242/dev.126.2.251.

Abstract

In C. elegans, the TGFbeta-like type II receptor daf-4 is required for two distinct signaling pathways. In association with the type I receptor daf-1, it functions in the dauer pathway. In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1. In an effort to determine how two different signals are transmitted through daf-4, we looked for other potential signaling partners for DAF-4. We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6. Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway. However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers, which demonstrates that the unique biological functions of daf-4 are mediated by distinct type I receptors functioning in parallel pathways. We propose that the C. elegans model for TGFbeta-like signaling, in which distinct type I receptors determine specificity, may be a general mechanism of achieving specificity in other organisms. These findings distinguish between the manner in which signaling specificity is achieved in TGFbeta-like pathways and receptor tyrosine-kinase (RTK) pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type I*
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Body Constitution / genetics
  • Body Patterning / genetics
  • Bone Morphogenetic Protein Receptors, Type I
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins*
  • Cloning, Molecular
  • Gene Expression Regulation, Developmental
  • Helminth Proteins / genetics
  • Male
  • Molecular Sequence Data
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics*
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Cell Surface / genetics*
  • Receptors, Growth Factor / genetics*
  • Receptors, Transforming Growth Factor beta / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Signal Transduction / genetics*
  • Tail / growth & development*
  • Transforming Growth Factor beta / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • SMA-6 protein, C elegans
  • Transforming Growth Factor beta
  • daf-4 protein, C elegans
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I

Associated data

  • GENBANK/AF104017