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Dual roles for patched in sequestering and transducing Hedgehog
1Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Cell
|November 1, 1996
Summary
The Hedgehog (Hh) protein binds to Patched (Ptc), activating Smoothened (Smo) and regulating animal development. Patched also limits Hh movement, creating a signaling range barrier.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Secreted Hedgehog (Hh) proteins are crucial for animal development.
- Smoothened (Smo) was recently proposed as a Hh receptor.
- The precise mechanism of Hh signal reception remains under investigation.
Purpose of the Study:
- To investigate the role of Patched (Ptc) in Hedgehog (Hh) signal reception.
- To elucidate the Hh signal transduction pathway involving Ptc and Smo.
- To understand how Ptc influences the range of Hh signaling.
Main Methods:
- Investigated protein interactions between Hh, Ptc, and Smo.
- Analyzed the functional consequences of Ptc expression on Hh signaling.
- Examined the effect of Ptc on Hh movement and distribution.
Main Results:
- Presented evidence implicating Patched (Ptc) in Hh reception.
- Suggested a novel mechanism where Hh binding to Ptc or a Ptc-Smo complex induces Smo activity.
- Demonstrated that Ptc limits Hh action by sequestering free Hh, creating a movement barrier.
Conclusions:
- Patched (Ptc) plays a key role in Hedgehog (Hh) signal reception.
- A novel signal transduction pathway involving Hh-Ptc interaction and subsequent Smo activation is proposed.
- Patched acts as a regulator of Hh signaling range, preventing excessive spread.
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