Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling.
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.
Gumienny
Tina L
TL
Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey, United States of America.
Macneil
Lesley
L
Zimmerman
Cole M
CM
Wang
Huang
H
Chin
Lena
L
Wrana
Jeffrey L
JL
Padgett
Richard W
RW
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
D019485:Bone Morphogenetic Proteins; D008565:Membrane Proteins