Research ArticleDevelopmental Biology

Self-Induced Patched Receptor Down-Regulation Modulates Cell Sensitivity to the Hedgehog Morphogen Gradient

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Science Signaling  24 Aug 2010:
Vol. 3, Issue 136, pp. ra63
DOI: 10.1126/scisignal.2001059

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Receptor Rheostat

The Hedgehog signaling pathway plays essential roles in cell fate specification and tissue patterning during development. The cellular response to this morphogen is complex because cells respond both to the absence of the ligand Hedgehog and to the presence of Hedgehog, with the cellular response a function of both the concentration of Hedgehog and the ratio of the Hedgehog-bound and unbound receptor Patched. Using the fly wing imaginal disc as a model system, Casali identified a mechanism by which Patched, which is transcriptionally induced in response to Hedgehog signaling, triggers its own down-regulation to maintain the appropriate balance of bound and unbound receptors. The mechanism did not require Hedgehog signaling per se, because both constitutively active and dominant-negative forms of the receptor induced the down-regulation. However, the Patched-induced decrease in abundance did require a ubiquitination motif in the C-terminal domain and the presence of internalization-competent receptors.

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