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Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells
Protein secretion is essential for epithelial tissue homoeostasis and therefore has to be tightly regulated. However, while the mechanisms regulating polarized protein sorting and trafficking have been widely studied in the past decade, those governing polarized secretion remain elusive. The calcium...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398874/ https://www.ncbi.nlm.nih.gov/pubmed/37163315 http://dx.doi.org/10.1091/mbc.E22-12-0549 |
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author | Liu, Dandan Paladino, Simona Zurzolo, Chiara Lebreton, Stéphanie |
author_facet | Liu, Dandan Paladino, Simona Zurzolo, Chiara Lebreton, Stéphanie |
author_sort | Liu, Dandan |
collection | PubMed |
description | Protein secretion is essential for epithelial tissue homoeostasis and therefore has to be tightly regulated. However, while the mechanisms regulating polarized protein sorting and trafficking have been widely studied in the past decade, those governing polarized secretion remain elusive. The calcium manganese pump SPCA1 and the calcium-binding protein Cab45 were recently shown to regulate the secretion of a subset of soluble cargoes in nonpolarized HeLa cells. Interestingly, we demonstrated that in polarized epithelial cells calcium levels in the trans-Golgi network (TGN), controlled by SPCA1, and Cab45 are critical for the apical sorting of glycosylphosphatidylinositol-anchored proteins (GPI-APs), a class of integral membrane proteins containing a soluble protein attached to the membrane by the GPI anchor, prompting us to investigate the mechanism regulating the polarized secretion of soluble cargoes. By reducing Cab45 expression level or overexpressing an inactive mutant of SPCA1, we found that Cab45 and calcium levels in the TGN drive the polarized apical secretion of a secretory form of placental alkaline phosphatase, exogenously expressed, and the endogenous soluble protein clusterin/Gp80 in Madin–Darby canine kidney (MDCK) cells. These data highlight the critical role of a calcium-dependent Cab45 mechanism regulating apical exocytosis in polarized MDCK cells. |
format | Online Article Text |
id | pubmed-10398874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103988742023-09-16 Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells Liu, Dandan Paladino, Simona Zurzolo, Chiara Lebreton, Stéphanie Mol Biol Cell Brief Reports Protein secretion is essential for epithelial tissue homoeostasis and therefore has to be tightly regulated. However, while the mechanisms regulating polarized protein sorting and trafficking have been widely studied in the past decade, those governing polarized secretion remain elusive. The calcium manganese pump SPCA1 and the calcium-binding protein Cab45 were recently shown to regulate the secretion of a subset of soluble cargoes in nonpolarized HeLa cells. Interestingly, we demonstrated that in polarized epithelial cells calcium levels in the trans-Golgi network (TGN), controlled by SPCA1, and Cab45 are critical for the apical sorting of glycosylphosphatidylinositol-anchored proteins (GPI-APs), a class of integral membrane proteins containing a soluble protein attached to the membrane by the GPI anchor, prompting us to investigate the mechanism regulating the polarized secretion of soluble cargoes. By reducing Cab45 expression level or overexpressing an inactive mutant of SPCA1, we found that Cab45 and calcium levels in the TGN drive the polarized apical secretion of a secretory form of placental alkaline phosphatase, exogenously expressed, and the endogenous soluble protein clusterin/Gp80 in Madin–Darby canine kidney (MDCK) cells. These data highlight the critical role of a calcium-dependent Cab45 mechanism regulating apical exocytosis in polarized MDCK cells. The American Society for Cell Biology 2023-07-01 /pmc/articles/PMC10398874/ /pubmed/37163315 http://dx.doi.org/10.1091/mbc.E22-12-0549 Text en © 2023 Liu et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License. |
spellingShingle | Brief Reports Liu, Dandan Paladino, Simona Zurzolo, Chiara Lebreton, Stéphanie Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title | Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title_full | Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title_fullStr | Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title_full_unstemmed | Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title_short | Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
title_sort | calcium-binding cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells |
topic | Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398874/ https://www.ncbi.nlm.nih.gov/pubmed/37163315 http://dx.doi.org/10.1091/mbc.E22-12-0549 |
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