A SURF4-to-proteoglycan relay mechanism that mediates the sorting and secretion of a tagged variant of sonic hedgehog

• DOI: 10.1073/pnas.2113991119
• Publication Date: 2022-03-10T19:14:57Z
• Authors: Xiao Tang; Rong Chen; Vince St Dollente...; Tingxuan Wang; Ying Wang; Kristina Poljak; Xinyu Fan; Hanchi Miao; Junjie Hu; Liang Zhang; Jinqing Huang; Shuhuai Yao; Elizabeth A. Miller; Yusong Guo
• Keywords: 570; 0303 health sciences; Membrane Proteins; Hedgehog Proteins/genetics; Biological Sciences; Proteoglycans/metabolism; Endoplasmic Reticulum; Protein Transport/physiology; Protein Transport; 03 medical and health sciences; Humans; Hedgehog Proteins; Proteoglycans; Membrane Proteins/genetics; Endoplasmic Reticulum/metabolism; Cargo receptor

Significance Sonic Hedgehog (Shh) is a key signaling molecule that plays important roles in embryonic patterning, cell differentiation, and organ development. Although fundamentally important, the molecular mechanisms that regulate secretion of newly synthesized Shh are still unclear. Our study reveals a role for the cargo receptor, SURF4, in facilitating export of Shh from the endoplasmic reticulum (ER) via a ER export signal. In addition, our study provides evidence suggesting that proteoglycans promote the dissociation of SURF4 from Shh at the Golgi, suggesting a SURF4-to-proteoglycan relay mechanism. These analyses provide insight into an important question in cell biology: how do cargo receptors capture their clients in one compartment, then disengage at their destination?