Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1.
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.
Incardona
J P
JP
Department of Biological Structure and Center for Developmental Biology, University of Washington, Seattle, WA 98195, USA.
Lee
J H
JH
Robertson
C P
CP
Enga
K
K
Kapur
R P
RP
Roelink
H
H
D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D053823:Hedgehog Proteins; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators; C070844:ptc protein, Drosophila; D020558:GTP Phosphohydrolases; D034281:Dynamins