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PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli
Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for the F-BAR domain protein PACSIN2 in normal mi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743356/ https://www.ncbi.nlm.nih.gov/pubmed/31390291 http://dx.doi.org/10.1091/mbc.E19-06-0352 |
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author | Postema, Meagan M. Grega-Larson, Nathan E. Meenderink, Leslie M. Tyska, Matthew J. |
author_facet | Postema, Meagan M. Grega-Larson, Nathan E. Meenderink, Leslie M. Tyska, Matthew J. |
author_sort | Postema, Meagan M. |
collection | PubMed |
description | Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for the F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule plays a role in controlling microvillar morphology. PACSIN2 KO enterocytes exhibit reduced numbers of microvilli and defects in the microvillar ultrastructure, with membranes lifting away from rootlets of core bundles. Dynamin2, a PACSIN2 binding partner, and other endocytic factors were also lost from their normal localization near microvillar rootlets. To determine whether loss of endocytic machinery could explain defects in microvillar morphology, we examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission fails, tubules are pulled into the cytoplasm and this, in turn, leads to a membrane-lifting phenomenon reminiscent of that observed at PACSIN2 KO brush borders. These findings lead to a new model where inward forces generated by endocytic machinery on the plasma membrane control the membrane wrapping of cell surface protrusions. |
format | Online Article Text |
id | pubmed-6743356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67433562019-11-16 PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli Postema, Meagan M. Grega-Larson, Nathan E. Meenderink, Leslie M. Tyska, Matthew J. Mol Biol Cell Articles Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for the F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule plays a role in controlling microvillar morphology. PACSIN2 KO enterocytes exhibit reduced numbers of microvilli and defects in the microvillar ultrastructure, with membranes lifting away from rootlets of core bundles. Dynamin2, a PACSIN2 binding partner, and other endocytic factors were also lost from their normal localization near microvillar rootlets. To determine whether loss of endocytic machinery could explain defects in microvillar morphology, we examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission fails, tubules are pulled into the cytoplasm and this, in turn, leads to a membrane-lifting phenomenon reminiscent of that observed at PACSIN2 KO brush borders. These findings lead to a new model where inward forces generated by endocytic machinery on the plasma membrane control the membrane wrapping of cell surface protrusions. The American Society for Cell Biology 2019-09-01 /pmc/articles/PMC6743356/ /pubmed/31390291 http://dx.doi.org/10.1091/mbc.E19-06-0352 Text en © 2019 Postema 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 Postema, Meagan M. Grega-Larson, Nathan E. Meenderink, Leslie M. Tyska, Matthew J. PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title | PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title_full | PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title_fullStr | PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title_full_unstemmed | PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title_short | PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
title_sort | pacsin2-dependent apical endocytosis regulates the morphology of epithelial microvilli |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743356/ https://www.ncbi.nlm.nih.gov/pubmed/31390291 http://dx.doi.org/10.1091/mbc.E19-06-0352 |
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