Caenorhabditis elegans SMA-10/lrig is a conserved transmembrane protein that enhances bone morphogenetic protein signaling

TY - JOUR

T1 - Caenorhabditis elegans SMA-10/lrig is a conserved transmembrane protein that enhances bone morphogenetic protein signaling

AU - Gumienny, Tina L.

AU - MacNeil, Lesley

AU - Zimmerman, Cole M.

AU - Wang, Huang

AU - Chin, Lena

AU - Wrana, Jeffrey L.

AU - Padgett, Richard W.

N1 - Funding Information: We would like to thank Y. Kohara (National Institute of Genetics, Mishima, Japan) for cDNAs; A. Fire (Stanford University) for expression vectors; the C. elegans genome consortium and A. Coulson (Wellcome Trust) for cosmids; B. Grant (Rutgers University), A. Singson (Rutgers University), and D. Winkelmann (UMDNJ) for microscopy assistance; R. Lints (Texas A&M University) and R. Schultz (TAMHSC-MCMD) for strains; R. Gleason, N. Patel, S. Kadakia, and R. Byrne for technical assistance; J. Lundgren for statistical assistance; and the Rutgers University/UMDNJ nematode community for helpful discussions. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (N.I.H.) National Center for Research Resources. This work is dedicated to A.L.G.

PY - 2010/5

Y1 - 2010/5

N2 - 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 immunoglobulinlike 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.

AB - 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 immunoglobulinlike 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.

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U2 - https://doi.org/10.1371/journal.pgen.1000963

DO - https://doi.org/10.1371/journal.pgen.1000963

M3 - Article

C2 - 20502686

VL - 6

SP - 16

JO - PLoS genetics

JF - PLoS genetics

SN - 1553-7390

IS - 5

ER -