气候变化领域集成服务门户(CCPortal): Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells

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DOI	10.1073/pnas.2014709118
	Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells
	Lebreton S.; Paladino S.; Liu D.; Nitti M.; von Blume J.; Pinton P.; Zurzolo C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Calcium; GPI-anchored proteins; Polarized epithelial cells; Protein clustering; Protein sorting
语种	英语
scopus关键词	adenosine triphosphatase (calcium); Cab45 protein; calcium; calcium binding protein; cholesterol; glycosylphosphatidylinositol anchored protein; manganese; secretory pathway Ca2+ ATPase pump type 1; unclassified drug; calcium; glycosylphosphatidylinositol anchored protein; ionomycin; animal cell; Article; controlled study; down regulation; epithelium cell; Golgi complex; MDCK cell line; molecular mechanics; nonhuman; oligomerization; polarization; protein targeting; trans Golgi network; animal; cell polarity; cluster analysis; dog; epithelium cell; gene expression regulation; gene knockdown; genetics; Golgi complex; metabolism; physiology; protein transport; Animals; Calcium; Cell Polarity; Cluster Analysis; Dogs; Epithelial Cells; Gene Expression Regulation; Gene Knockdown Techniques; Golgi Apparatus; GPI-Linked Proteins; Ionomycin; Madin Darby Canine Kidney Cells; Protein Transport
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251068
作者单位	Institut Pasteur, Unité de Trafic Membranaire et Pathogénèse, Paris, 75015, France; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, 80131, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, 44121, Italy; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Lebreton S.,Paladino S.,Liu D.,et al. Calcium levels in the Golgi complex regulate clustering and apical sorting of GPI-APs in polarized epithelial cells[J],2021,118(33).
APA	Lebreton S..,Paladino S..,Liu D..,Nitti M..,von Blume J..,...&Zurzolo C..(2021).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,118(33).
MLA	Lebreton S.,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 118.33(2021).