Work

Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1

Year: 2000

Type: article

Abstract: Patched (Ptc) is the ligand-binding component of the Hedgehog (Hh) receptor complex. In the Drosophila embryo, Ptc and Hh colocalize in vesicular punctate structures. However, receptor-mediated endocytosis of Hh proteins has not been demonstrated. By using chick neural plate explants, we show that Sonic hedgehog (Shh)-responsive neural precursor cells internalize recombinant and endogenous Shh and provide direct evidence for a gradient of endogenous Shh in the ventral neural tube. Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc-binding site of Shh. These findings suggest that Shh internalization is mediated by Ptc-1 and may be linked to signaling. Concordantly, transfection of mammalian cell lines with a Ptc-1 cDNA confers the ability to internalize multiple forms of Shh, including transmembrane-anchored Shh, by a dynamin-dependent process.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.220251997

Authors: John P. Incardona, Ju Ho Lee, Christie P. Robertson, Kristi Enga, Raj P. Kapur, Henk Roelink

Institutions: University of Washington, European Molecular Biology Laboratory, European Molecular Biology Laboratory

Language: English

Topic: Hedgehog Signaling Pathway Studies

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: McKnight Foundation, University of Washington, National Institute of Environmental Health Sciences

Awards: G5120127474, University of Washington Interdisciplinary Center for Exposures, Diseases, Genomics & Environment