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


ABSTRACT: SignificanceSonic 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?

SUBMITTER: Tang X 

PROVIDER: S-EPMC8931250 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Tang Xiao X   Chen Rong R   Mesias Vince St Dollente VSD   Wang Tingxuan T   Wang Ying Y   Poljak Kristina K   Fan Xinyu X   Miao Hanchi H   Hu Junjie J   Zhang Liang L   Huang Jinqing J   Yao Shuhuai S   Miller Elizabeth A EA   Guo Yusong Y  

Proceedings of the National Academy of Sciences of the United States of America 20220310 11


SignificanceSonic 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 proteoglycan  ...[more]

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