What role does cholesterol play in Hedgehog protein processing?
Hedgehog proteins undergo unique autoprocessing requiring intein-like activity and lipid modifications for gradient formation. C-terminal domain cleaves N-terminal signaling peptide, covalently attaches cholesterol to C-terminus, and palmitate attaches to N-terminal cysteine via Skinny hedgehog HHAT acyltransferase in endoplasmic reticulum. Cholesterol moiety anchors Hedgehog to membranes of producing cells, restricts diffusion, enables multimeric sterol-rich puncta for long-range gradient and facilitates secretion via Dispatched transporter RND protein requiring sterol sensing domain. Without
Ref: Porter et al., Science 1996: Cholesterol modification of Hedgehog required for secretion, multimerization and gradient.
