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Updated: Jan 31, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

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Patched1-ArhGAP36-PKA-Inversin axis determines the ciliary translocation of Smoothened for Sonic Hedgehog pathway

Boyan Zhang1, Tenghan Zhuang1, Qiaoyu Lin1

  • 1Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, 100871 Beijing, China.

Proceedings of the National Academy of Sciences of the United States of America
|January 2, 2019
PubMed

Insights

The Sonic Hedgehog (Shh) pathway

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • The Sonic Hedgehog (Shh) pathway is crucial for cell proliferation, development, and cancer.
  • Shh signaling activation occurs in the primary cilium, involving Patched1 and Smoothened.
  • The precise mechanism coupling Patched1 activity to Smoothened translocation remains unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism regulating Smoothened translocation into the primary cilium.
  • To identify key proteins involved in the initial steps of Sonic Hedgehog pathway activation.

Main Methods:

  • Investigated protein-protein interactions using co-immunoprecipitation.
  • Utilized knockdown experiments to assess the role of Inversin.
  • Analyzed protein localization via immunofluorescence microscopy.

Main Results:

  • Identified a novel Patched1-ArhGAP36-PKA-Inversin signaling axis.
  • Demonstrated that Patched1 stabilizes ArhGAP36 at the centrosome.
  • Showed that Shh pathway activation leads to ArhGAP36 removal, PKA accumulation, and Inversin phosphorylation, promoting Smoothened ciliary translocation.

Conclusions:

  • The Patched1-ArhGAP36-PKA-Inversin axis is essential for Smoothened ciliary translocation.
  • This pathway represents a key regulatory mechanism for initiating Shh signaling.
Keywords:
InversinPKAPatched1SmoothenedSonic Hedgehog pathway

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