Numb positively regulates Hedgehog signaling at the ciliary pocket

Numb positively regulates Hedgehog signaling at the ciliary pocket

Blog Article

Abstract Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell.Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling.Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from Compositi Matrix Toe Cage the cilium, a key step in Hh signaling activation.Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling.

Numb loss in spinal neural progenitors reduces Shh-induced Scalp Scrub differentiation into cell fates reliant on high Hh activity.Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size.This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.