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Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels
The endoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to ion and lipid signaling and homeostasis. The Kv2.1 ion channel is localized at ER–PM junctions in brain neurons and is unique among PM proteins in its ability to remodel these specialized membrane contact sites. Here,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233057/ https://www.ncbi.nlm.nih.gov/pubmed/30091655 http://dx.doi.org/10.1091/mbc.E18-05-0337 |
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author | Kirmiz, Michael Palacio, Stephanie Thapa, Parashar King, Anna N. Sack, Jon T. Trimmer, James S. |
author_facet | Kirmiz, Michael Palacio, Stephanie Thapa, Parashar King, Anna N. Sack, Jon T. Trimmer, James S. |
author_sort | Kirmiz, Michael |
collection | PubMed |
description | The endoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to ion and lipid signaling and homeostasis. The Kv2.1 ion channel is localized at ER–PM junctions in brain neurons and is unique among PM proteins in its ability to remodel these specialized membrane contact sites. Here, we show that this function is conserved between Kv2.1 and Kv2.2, which differ in their biophysical properties, modulation, and cellular expression. Kv2.2 ER–PM junctions are present at sites deficient in the actin cytoskeleton, and disruption of the actin cytoskeleton affects their spatial organization. Kv2.2-containing ER–PM junctions overlap with those formed by canonical ER–PM tethers. The ability of Kv2 channels to remodel ER–PM junctions is unchanged by point mutations that eliminate their ion conduction but eliminated by point mutations within the Kv2-specific proximal restriction and clustering (PRC) domain that do not impact their ion channel function. The highly conserved PRC domain is sufficient to transfer the ER–PM junction–remodeling function to another PM protein. Last, brain neurons in Kv2 double-knockout mice have altered ER–PM junctions. Together, these findings demonstrate a conserved in vivo function for Kv2 family members in remodeling neuronal ER–PM junctions that is distinct from their canonical role as ion-conducting channels shaping neuronal excitability. |
format | Online Article Text |
id | pubmed-6233057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62330572018-12-16 Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels Kirmiz, Michael Palacio, Stephanie Thapa, Parashar King, Anna N. Sack, Jon T. Trimmer, James S. Mol Biol Cell Articles The endoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to ion and lipid signaling and homeostasis. The Kv2.1 ion channel is localized at ER–PM junctions in brain neurons and is unique among PM proteins in its ability to remodel these specialized membrane contact sites. Here, we show that this function is conserved between Kv2.1 and Kv2.2, which differ in their biophysical properties, modulation, and cellular expression. Kv2.2 ER–PM junctions are present at sites deficient in the actin cytoskeleton, and disruption of the actin cytoskeleton affects their spatial organization. Kv2.2-containing ER–PM junctions overlap with those formed by canonical ER–PM tethers. The ability of Kv2 channels to remodel ER–PM junctions is unchanged by point mutations that eliminate their ion conduction but eliminated by point mutations within the Kv2-specific proximal restriction and clustering (PRC) domain that do not impact their ion channel function. The highly conserved PRC domain is sufficient to transfer the ER–PM junction–remodeling function to another PM protein. Last, brain neurons in Kv2 double-knockout mice have altered ER–PM junctions. Together, these findings demonstrate a conserved in vivo function for Kv2 family members in remodeling neuronal ER–PM junctions that is distinct from their canonical role as ion-conducting channels shaping neuronal excitability. The American Society for Cell Biology 2018-10-01 /pmc/articles/PMC6233057/ /pubmed/30091655 http://dx.doi.org/10.1091/mbc.E18-05-0337 Text en © 2018 Kirmiz 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 Kirmiz, Michael Palacio, Stephanie Thapa, Parashar King, Anna N. Sack, Jon T. Trimmer, James S. Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title | Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title_full | Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title_fullStr | Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title_full_unstemmed | Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title_short | Remodeling neuronal ER–PM junctions is a conserved nonconducting function of Kv2 plasma membrane ion channels |
title_sort | remodeling neuronal er–pm junctions is a conserved nonconducting function of kv2 plasma membrane ion channels |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233057/ https://www.ncbi.nlm.nih.gov/pubmed/30091655 http://dx.doi.org/10.1091/mbc.E18-05-0337 |
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