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Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells
The repair (sealing) of plasmalemmal damage, consisting of small holes to complete transections, is critical for cell survival, especially for neurons that rarely regenerate cell bodies. We first describe and evaluate different measures of cell sealing. Some measures, including morphological/ultra-s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994430/ https://www.ncbi.nlm.nih.gov/pubmed/27630671 http://dx.doi.org/10.4103/1673-5374.187019 |
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author | Bittner, George D. Spaeth, Christopher S. Poon, Andrew D. Burgess, Zachary S. McGill, Christopher H. |
author_facet | Bittner, George D. Spaeth, Christopher S. Poon, Andrew D. Burgess, Zachary S. McGill, Christopher H. |
author_sort | Bittner, George D. |
collection | PubMed |
description | The repair (sealing) of plasmalemmal damage, consisting of small holes to complete transections, is critical for cell survival, especially for neurons that rarely regenerate cell bodies. We first describe and evaluate different measures of cell sealing. Some measures, including morphological/ultra-structural observations, membrane potential, and input resistance, provide very ambiguous assessments of plasmalemmal sealing. In contrast, measures of ionic current flow and dye barriers can, if appropriately used, provide more accurate assessments. We describe the effects of various substances (calcium, calpains, cytoskeletal proteins, ESCRT proteins, mUNC-13, NSF, PEG) and biochemical pathways (PKA, PKC, PLC, Epac, cytosolic oxidation) on plasmalemmal sealing probability, and suggest that substances, pathways, and cellular events associated with plasmalemmal sealing have undergone a very conservative evolution. During sealing, calcium ion influx mobilizes vesicles and other membranous structures (lysosomes, mitochondria, etc.) in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to minutes. Furthermore, we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets, or in a single step involving the fusion of one large wound vesicle with the nearby, undamaged plasmalemma. We describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the perikaryon. Finally, we speculate on relationships between plasmalemmal sealing, Wallerian degeneration, and the ability of polyethylene glycol (PEG) to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves. A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develop treatments for traumatic nerve injuries, stroke, muscular dystrophy, and other pathologies. |
format | Online Article Text |
id | pubmed-4994430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49944302016-09-14 Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells Bittner, George D. Spaeth, Christopher S. Poon, Andrew D. Burgess, Zachary S. McGill, Christopher H. Neural Regen Res Invited Review The repair (sealing) of plasmalemmal damage, consisting of small holes to complete transections, is critical for cell survival, especially for neurons that rarely regenerate cell bodies. We first describe and evaluate different measures of cell sealing. Some measures, including morphological/ultra-structural observations, membrane potential, and input resistance, provide very ambiguous assessments of plasmalemmal sealing. In contrast, measures of ionic current flow and dye barriers can, if appropriately used, provide more accurate assessments. We describe the effects of various substances (calcium, calpains, cytoskeletal proteins, ESCRT proteins, mUNC-13, NSF, PEG) and biochemical pathways (PKA, PKC, PLC, Epac, cytosolic oxidation) on plasmalemmal sealing probability, and suggest that substances, pathways, and cellular events associated with plasmalemmal sealing have undergone a very conservative evolution. During sealing, calcium ion influx mobilizes vesicles and other membranous structures (lysosomes, mitochondria, etc.) in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to minutes. Furthermore, we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets, or in a single step involving the fusion of one large wound vesicle with the nearby, undamaged plasmalemma. We describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the perikaryon. Finally, we speculate on relationships between plasmalemmal sealing, Wallerian degeneration, and the ability of polyethylene glycol (PEG) to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves. A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develop treatments for traumatic nerve injuries, stroke, muscular dystrophy, and other pathologies. Medknow Publications & Media Pvt Ltd 2016-07 /pmc/articles/PMC4994430/ /pubmed/27630671 http://dx.doi.org/10.4103/1673-5374.187019 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Invited Review Bittner, George D. Spaeth, Christopher S. Poon, Andrew D. Burgess, Zachary S. McGill, Christopher H. Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title | Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title_full | Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title_fullStr | Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title_full_unstemmed | Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title_short | Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
title_sort | repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells |
topic | Invited Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994430/ https://www.ncbi.nlm.nih.gov/pubmed/27630671 http://dx.doi.org/10.4103/1673-5374.187019 |
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