| Authors |
Ramazanov BR, Parchure A, Di Martino R, Kumar A, Chung M, Kim Y, Griesbeck O,
Schwartz MA, Luini A, von Blume J
|
| Submitted By |
Julia von Blume on 10/8/2024 |
| Status |
Published |
| Journal |
Molecular biology of the cell |
| Year |
2024 |
| Date Published |
4/1/2024 |
| Volume : Pages |
35 : ar50 |
| PubMed Reference |
38294859 |
| Abstract |
Ca2+ influx into the trans-Golgi Network (TGN) promotes secretory cargo sorting
by the Ca2+-ATPase SPCA1 and the luminal Ca2+ binding protein Cab45. Cab45
oligomerizes upon local Ca2+ influx, and Cab45 oligomers sequester and separate
soluble secretory cargo from the bulk flow of proteins in the TGN. However, how
this Ca2+ flux into the lumen of the TGN is achieved remains mysterious, as the
cytosol has a nanomolar steady-state Ca2+ concentration. The TGN forms membrane
contact sites (MCS) with the Endoplasmic Reticulum (ER), allowing
protein-mediated exchange of molecular species such as lipids. Here, we show
that the TGN export of secretory proteins requires the integrity of ER-TGN MCS
and inositol 3 phosphate receptor (IP3R)-dependent Ca2+ fluxes in the MCS,
suggesting Ca2+ transfer between these organelles. Using an MCS-targeted Ca2+
FRET sensor module, we measure the Ca2+ flow in these sites in real time. These
data show that ER-TGN MCS facilitates the Ca2+ transfer required for
Ca2+-dependent cargo sorting and export from the TGN, thus solving a fundamental
question in cell biology.
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