The ihog cell-surface proteins bind Hedgehog and mediate pathway activation

Shenqin Yao; Lawrence Lum; Philip Beachy

doi:10.1016/j.cell.2006.02.040

The ihog cell-surface proteins bind Hedgehog and mediate pathway activation

Cell. 2006 Apr 21;125(2):343-57. doi: 10.1016/j.cell.2006.02.040.

Authors

Shenqin Yao¹, Lawrence Lum, Philip Beachy

Affiliation

¹ Howard Hughes Medical Institute, Departments of Molecular Biology, Genetics, and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

PMID: 16630821
DOI: 10.1016/j.cell.2006.02.040

Abstract

The ihog gene (interference hedgehog), identified by RNA interference in Drosophila cultured cells, encodes a type 1 membrane protein shown here to bind and to mediate response to the active Hedgehog (Hh) protein signal. ihog mutations produce defects characteristic of Hh signaling loss in embryos and imaginal discs, and epistasis analysis places ihog action at or upstream of the negatively acting receptor component, Patched (Ptc). The first of two extracellular fibronectin type III (FNIII) domains of the Ihog protein mediates a specific interaction with Hh protein in vitro, but the second FNIII domain is additionally required for in vivo signaling activity and for Ihog-enhanced binding of Hh protein to cells coexpressing Ptc. Other members of the Ihog family, including Drosophila Boi and mammalian CDO and BOC, also interact with Hh ligands via a specific FNIII domain, thus identifying an evolutionarily conserved family of membrane proteins that function in Hh signal response.

MeSH terms

Animals
Body Patterning / genetics
Cells, Cultured
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster
Embryo, Nonmammalian / anatomy & histology
Embryo, Nonmammalian / physiology
Embryonic Structures / anatomy & histology
Embryonic Structures / physiology
Fibronectins / metabolism
Hedgehog Proteins
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Membrane Proteins / genetics
Membrane Proteins / metabolism
Protein Binding
Protein Structure, Tertiary
Proteoglycans / metabolism
RNA Interference*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Signal Transduction / physiology*
Trans-Activators / genetics
Trans-Activators / metabolism

Substances

Drosophila Proteins
Fibronectins
Hedgehog Proteins
Membrane Glycoproteins
Membrane Proteins
Proteoglycans
Receptors, Cell Surface
Trans-Activators
dlp protein, Drosophila
iHog protein, Drosophila
ptc protein, Drosophila
hh protein, Drosophila