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EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells

Dense-core vesicles (DCVs) are secretory vesicles found in neurons and endocrine cells. DCVs package and release cargoes including neuropeptides, biogenic amines, and peptide hormones. We recently identified the endosome-associated recycling protein (EARP) complex and the EARP-interacting-protein EI...

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Autores principales: Topalidou, Irini, Cattin-Ortolá, Jérôme, Hummer, Blake, Asensio, Cedric S., Ailion, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938272/
https://www.ncbi.nlm.nih.gov/pubmed/31721635
http://dx.doi.org/10.1091/mbc.E18-07-0469
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author Topalidou, Irini
Cattin-Ortolá, Jérôme
Hummer, Blake
Asensio, Cedric S.
Ailion, Michael
author_facet Topalidou, Irini
Cattin-Ortolá, Jérôme
Hummer, Blake
Asensio, Cedric S.
Ailion, Michael
author_sort Topalidou, Irini
collection PubMed
description Dense-core vesicles (DCVs) are secretory vesicles found in neurons and endocrine cells. DCVs package and release cargoes including neuropeptides, biogenic amines, and peptide hormones. We recently identified the endosome-associated recycling protein (EARP) complex and the EARP-interacting-protein EIPR-1 as proteins important for controlling levels of DCV cargoes in Caenorhabditis elegans neurons. Here we determine the role of mammalian EIPR1 in insulinoma cells. We find that in Eipr1 KO cells, there is reduced insulin secretion, and mature DCV cargoes such as insulin and carboxypeptidase E (CPE) accumulate near the trans-Golgi network and are not retained in mature DCVs in the cell periphery. In addition, we find that EIPR1 is required for the stability of the EARP complex subunits and for the localization of EARP and its association with membranes, but EIPR1 does not affect localization or function of the related Golgi-associated retrograde protein (GARP) complex. EARP is localized to two distinct compartments related to its function: an endosomal compartment and a DCV biogenesis-related compartment. We propose that EIPR1 functions with EARP to control both endocytic recycling and DCV maturation.
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spelling pubmed-69382722020-03-16 EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells Topalidou, Irini Cattin-Ortolá, Jérôme Hummer, Blake Asensio, Cedric S. Ailion, Michael Mol Biol Cell Articles Dense-core vesicles (DCVs) are secretory vesicles found in neurons and endocrine cells. DCVs package and release cargoes including neuropeptides, biogenic amines, and peptide hormones. We recently identified the endosome-associated recycling protein (EARP) complex and the EARP-interacting-protein EIPR-1 as proteins important for controlling levels of DCV cargoes in Caenorhabditis elegans neurons. Here we determine the role of mammalian EIPR1 in insulinoma cells. We find that in Eipr1 KO cells, there is reduced insulin secretion, and mature DCV cargoes such as insulin and carboxypeptidase E (CPE) accumulate near the trans-Golgi network and are not retained in mature DCVs in the cell periphery. In addition, we find that EIPR1 is required for the stability of the EARP complex subunits and for the localization of EARP and its association with membranes, but EIPR1 does not affect localization or function of the related Golgi-associated retrograde protein (GARP) complex. EARP is localized to two distinct compartments related to its function: an endosomal compartment and a DCV biogenesis-related compartment. We propose that EIPR1 functions with EARP to control both endocytic recycling and DCV maturation. The American Society for Cell Biology 2020-01-01 /pmc/articles/PMC6938272/ /pubmed/31721635 http://dx.doi.org/10.1091/mbc.E18-07-0469 Text en © 2020 Topalidou, Cattin-Ortolá, 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. http://creativecommons.org/licenses/by-nc-sa/3.0 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 3.0 Unported Creative Commons License.
spellingShingle Articles
Topalidou, Irini
Cattin-Ortolá, Jérôme
Hummer, Blake
Asensio, Cedric S.
Ailion, Michael
EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title_full EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title_fullStr EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title_full_unstemmed EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title_short EIPR1 controls dense-core vesicle cargo retention and EARP complex localization in insulin-secreting cells
title_sort eipr1 controls dense-core vesicle cargo retention and earp complex localization in insulin-secreting cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938272/
https://www.ncbi.nlm.nih.gov/pubmed/31721635
http://dx.doi.org/10.1091/mbc.E18-07-0469
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