12th May 08

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Components of Hedgehog Signalling

Slmb Supernumerary Limbs

Slmb is the protein Supernumerary limbs. It is a subunit of a multi-protein complex involved in targeting proteins for degradation via the ubiquitin-proteasome pathway (an important pathway in controlling the abundance of proteins in eukaryotes). Slmb regulates several developmental pathways, including Hh. Loss of slmb function leads to accumulation of high levels of Ci and the ectopic expression of the Hh gene.

Cos2 Costal2

Costal2 is a kinesin like protein that acts as a repressor in the hedgehog signalling pathway. It is located in the cytoplasm and forms both a trimeric cytoplasmic complex with Fu and Ci, in addition to a tetrameric cytoplasmic complex with the binding of Su(fu) to Fu and Ci. Cos2 is able to bind microtubules as required in the trimeric complex.

Cos2 binds Ci in the cytoplasm, until Hh reverses the binding and Ci is released into the nucleus to function as a transcription factor. This is suggestive of a controlling role played by Cos2 on the transcription factor, Ci.

Kinesins are enzymes that convert energy from ATP hydrolysis into mechanical force to move long microtubules.

Protein Structure: Structurally, the Cos2 protein is predicted to be globular formed by alternating alpha helices and beta sheets of the N-terminal (residues 1-450) and the C-terminal (residues 1050-1201) regions. The central region (residues 643-990) structures a parallel coiled coil containing 36 heptad repeats forming a stable homodimer. The image below shows the predicted structure of Cos2 and has been adapted from Sissons, J.C., 1997 Cell(90) 235-245.

Predicted Structure of Cos2

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