Sac1 degron A431 cells 3h DMSO vs 3h IAA

ABSTRACT: Sac1 is a conserved phosphoinositide phosphatase, whose loss-of-function compromises cell and organism viability. Here, we employed acute auxin-inducible Sac1 degradation to identify its immediate downstream effectors in human cells. Most of Sac1 was is degraded in ~1 h, paralleled by increased PI(4)P and decreased cholesterol in the trans-Golgi network (TGN) during the following hour, and superseded by Golgi fragmentation, impaired glycosylation, and selective degradation of TGN proteins by ~4 h. The TGN disintegration resulted from its acute deacidification caused by disassembly of the Golgi V-ATPase. Mechanistically, Sac1 mediated TGN membrane composition maintained an assembly-promoting conformation of the V0a2 subunit. Key phenotypes of acute Sac1 degradation were are recapitulated in human differentiated trophoblasts, causing processing defects of chorionic gonadotropin, in line with loss-of-function intolerance of the human SACML1 gene. Collectively, our findings reveal that the assembly of the Golgi V-ATPase is controlled by the TGN membrane via Sac1 fuelled lipid exchange.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Miesje van der Stoel  

LAB HEAD: Elina Ikonen

PROVIDER: PXD065794 | Pride | 2025-07-08

REPOSITORIES: Pride