title: Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling.
abstract: Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP-like receptor signaling. SMA-10 acts genetically in a BMP-like (Sma/Mab) pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf) animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors.
authors.affiliation: Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Gumienny
authors.forename: Lesley
authors.initials: L
authors.lastname: Macneil
authors.forename: Cole M
authors.initials: CM
authors.lastname: Zimmerman
authors.forename: Huang
authors.initials: H
authors.lastname: Wang
authors.forename: Lena
authors.initials: L
authors.lastname: Chin
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
authors.forename: Richard W
authors.initials: RW
authors.lastname: Padgett
mesh_terms: D000483:Alleles; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000502:physiology*; D017124:Conserved Sequence; D008565:Membrane Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins