Practice question

Wnt activity modulated by extracellular modifiers controlling lipidation state and receptor availability. Notum encodes secreted carboxylesterase pectin acetylesterase-like deacylase related to lipases that specifically cleaves palmitoleate moiety added by Porcupine O-acyltransferase in ER on Wnt Ser209, essential for Frizzled binding hydrophobic groove. Removal of lipid blocks receptor engagement, dampening signal, shaping gradient. Axin and APC are intracellular negative regulators scaffolding destruction complex; Dishevelled is positive adaptor. Notum secreted from Wnt target tissue itself forms feedback inhibition loop refining gradient and preventing ectopic signaling in Drosophila wing disc and vertebrate intestinal crypt homeostasis.