ABIO303: Signaling Pathways

What are the receptors in canonical Wnt signaling?

- Frizzled and LRP5/6.

What happens in canonical Wnt signaling when Wnt binds?

- The destruction complex is inhibited, leading to β-catenin stabilization and nuclear translocation, where it activates transcription.

What happens in the absence of Wnt?

- β-catenin is phosphorylated and degraded by the APC-Axin-GSK3β complex.

What does the non-canonical Wnt pathway (Planar Cell Polarity) regulate?

- Cytoskeletal remodeling, cell polarity, and migration via JNK, Rho, and Rac pathways — not gene transcription.

What is the role of Notum in Wnt signaling?

- Acts as a negative feedback regulator, inactivating Wnt by removing its lipid modification.

What is the role of Wnt4?

- Involved in sex determination (ovary development) and kidney formation.

Key components of the Hedgehog pathway?

- Patched (PTCH), Smoothened (SMO), and Gli/Ci transcription factors.

What happens in the absence of Hedgehog?

- Patched inhibits Smoothened, leading to Gli/Ci cleavage into repressor forms that inhibit target genes.

What happens when Hedgehog binds?

- Smoothened is activated, preventing Gli/Ci cleavage → Gli acts as an activator, turning on target genes.

What is the primary cilium's role in Hedgehog signaling?

- It serves as the signaling hub where Smoothened and Gli proteins localize for pathway activation.

What type of signaling is Notch?

- Juxtacrine signaling — requires direct cell-cell contact.

What are the core components of the Notch pathway?

- Delta (ligand) on one cell binds Notch (receptor) on another.

What happens after Delta-Notch binding?

- Notch receptor is cleaved, releasing the Notch Intracellular Domain (NICD), which moves to the nucleus to regulate gene expression.

What enzyme is responsible for Notch receptor cleavage?

- Presenilin, part of the γ-secretase complex.

What is FGFR3's role in development?

- Regulates bone growth and skeletal development.

What causes Thanatophoric dysplasia?

- Gain-of-function (activating) mutations in FGFR3, leading to premature growth plate closure and skeletal abnormalities.

What is the transcriptional complex activated by BMP signaling?

- Smad1/5 + Smad4 complex → activates target gene transcription.

What influences paracrine signal diffusion?

- The extracellular matrix (ECM), receptor density, and stabilizing molecules.

What are cytonemes?

- Thin, actin-based filopodia that transport signaling molecules directly between cells.

What do heparan sulfate proteoglycans (HSPGs) do?

- Stabilize, bind, and restrict diffusion of morphogens like Wnt, FGF, and Hedgehog to form precise gradients.