Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2021

Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells

(1) , (2) , (1) , (2, 3) , (4) , (3) , (1)
1
2
3
4

Abstract

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid-associated luminal secretory cargoes selectively sorted to the apical surface of the epithelia where they reside and play diverse vital functions. Cholesterol-dependent clustering of GPI-APs in the Golgi is the key step driving their apical sorting and their further plasma membrane organization and activity; however, the specific machinery involved in this Golgi event is still poorly understood. In this study, we show that the formation of GPI-AP homoclusters (made of single GPI-AP species) in the Golgi relies directly on the levels of calcium within cisternae. We further demonstrate that the TGN calcium/manganese pump, SPCA1, which regulates the calcium concentration within the Golgi, and Cab45, a calcium-binding luminal Golgi resident protein, are essential for the formation of GPI-AP homoclusters in the Golgi and for their subsequent apical sorting. Down-regulation of SPCA1 or Cab45 in polarized epithelial cells impairs the oligomerization of GPI-APs in the Golgi complex and leads to their missorting to the basolateral surface. Overall, our data reveal an unexpected role for calcium in the mechanism of GPI-AP apical sorting in polarized epithelial cells and identify the molecular machinery involved in the clustering of GPI-APs in the Golgi.

Dates and versions

pasteur-03517396 , version 1 (07-01-2022)

Identifiers

Cite

Stephanie Lebreton, Simona Paladino, Dandan Liu, Maria Nitti, Julia von Blume, et al.. Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (33), pp.e2014709118. ⟨10.1073/pnas.2014709118⟩. ⟨pasteur-03517396⟩
20 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More