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#Hedgehog pathway

6 public questions tagged with this topic.

Paracrine Factor

Which protein is critical for the activation of Gli transcription factors in the Hedgehog pathway?

Hedgehog-dependent activation of Gli transcription factors requires regulated processing and ciliary trafficking mechanisms. In absence of Hedgehog, Gli2 and Gli3 phosphorylated by PKA, GSK3, CK1 create phosphodegron recognized by beta-TrCP SCF E3 ligase and Sufu sequestration, cleaved to repressor forms Gli3R blocking targets like Patched1, Hhip1. Hedgehog binding to Patched derepresses Smoothened, which accumulates in primary cilium, binds EVC2, inhibits Suppressor of Fused, stabilizing full-length Gli as activator GliA. This Smoothened-dependent conversion in cilium tip, requiring kinesin K

Ref: Huangfu & Anderson, Development 2006: Smoothened ciliary localization required for Gli activator formation in Hedgehog pathway.

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Paracrine Factor

What is the function of the Smoothened (Smo) receptor in the Hedgehog signaling pathway?

Smoothened is seven-transmembrane protein homologous to G protein-coupled receptors, acting as obligate transducer of Hedgehog signaling downstream of Patched. In absence of Hedgehog, Patched twelve-pass transporter inhibits Smoothened by preventing ciliary accumulation, promoting cholesterol transport imbalance and internalization. Hedgehog binding to Patched via lipoprotein particles relieves inhibition, allowing Smoothened to translocate to primary cilium tip, activate heterotrimeric Gi proteins, suppress Sufu-Gli sequestration, leading to Gli activator formation. It does not directly bind

Ref: Ingham & McMahon, Genes & Development 2001: Smoothened as obligate transducer derepressed when Patched binds Hedgehog.

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Cell Signaling Dev Bio & Other Pathways

Hedgehog misregulation can lead to

Developmental defects, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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Cell Signaling Dev Bio & Other Pathways

Transcription factor in Drosophila Hedgehog pathway is

Ci, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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Cell Signaling Dev Bio & Other Pathways

Smoothened is structurally similar to

GPCRs, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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Cell Signaling Dev Bio & Other Pathways

Patched receptor normally inhibits

Smoothened, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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