Open AccessA SURF4-to-proteoglycan relay mechanism that mediates the sorting and secretion of a tagged variant of sonic hedgehog
Author(s) -
Xiao Song Tang,
Rong Chen,
Vince St. Dollente Mesias,
Tingxuan Wang,
Ying Wang,
Kristina Poljak,
Xinyu Fan,
Miao Hua,
Junjie Hu,
Liang Zhang,
Jinqing Huang,
Shuhuai Yao,
Elizabeth A. Miller,
Yusong Guo
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2113991119
Subject(s) - sonic hedgehog , microbiology and biotechnology , secretion , morphogen , endoplasmic reticulum , hedgehog , proteoglycan , golgi apparatus , receptor , biology , hedgehog signaling pathway , signal transduction , live cell imaging , cell , genetics , biochemistry , gene , extracellular matrix
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?