Xiaoliang Liu, Patricia T Yam, Sabrina Schlienger, Eva Cai, Jingyi Zhang, Wei-Ju Chen, Oscar Torres Gutierrez, Vanesa Jimenez Amilburu, Vasanth Ramamurthy, Alice Y Ting, Tess C Branon, Michel Cayouette, Risako Gen, Tessa Marks, Jennifer H Kong, Frédéric Charron, Xuecai Ge
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 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...
April 25, 2024: Nature Communications