GRIA1 regulates TGN export and secretion of Sonic hedgehog.

ABSTRACT: Sonic hedgehog (Shh) signaling orchestrates diverse developmental processes in metazoans and is implicated in numerous human diseases. While downstream signaling in recipient cells have been extensively characterized, the mechanisms governing secretion of newly synthesized Shh from producer cells remain less well understood. Building on our previous identification of a Surfeit locus protein 4 (SURF4)-to-proteoglycan (PG) relay mechanism that mediates endoplasmic reticulum (ER)-to-Golgi transport of the N-terminal Shh fragment (ShhN), we investigated ShhN export from the trans-Golgi network (TGN). We show that ShhN exits the TGN via a clathrin-dependent secretory pathway. Mechanistic analyses identify the transmembrane protein glutamate receptor 1 (GRIA1) as a key mediator: GRIA1 associates

SUBMITTER: Tang X 

PROVIDER: S-EPMC12858347 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature