Eintrag weiter verarbeiten
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts
Gespeichert in:
| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | The Journal of Neuroscience, 34, 2014, 48, S. 16140-16152 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
|
| Schlagwörter: |
| author_facet |
Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia |
|---|---|
| author |
Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia |
| spellingShingle |
Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia The Journal of Neuroscience PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts General Neuroscience |
| author_sort |
lee, sooyeon |
| spelling |
Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1908-14.2014 <jats:p>Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions. Using<jats:italic>in vitro</jats:italic>models, we discovered that, in the absence of PMP22, the migration and adhesion capacity of Schwann cells and fibroblasts are similarly impaired. Furthermore, PMP22-deficient Schwann cells produce shortened myelin internodes, and display compressed axial cell length and collapsed lamellipodia. During early postnatal development, F-actin-enriched Schmidt-Lanterman incisures do not form properly in nerves from PMP22<jats:sup>−/−</jats:sup>mice, and the expression and localization of molecules associated with uncompacted myelin domains and lipid rafts, including flotillin-1, cholesterol, and GM1 ganglioside, are altered. In addition, we identified changes in the levels and distribution of cholesterol and ApoE when PMP22 is absent. Significantly, cholesterol supplementation of the culture medium corrects the elongation and migration deficits of PMP22<jats:sup>−/−</jats:sup>Schwann cells, suggesting that the observed functional impairments are directly linked with cholesterol deficiency of the plasma membrane. Our findings support a novel role for PMP22 in the linkage of the actin cytoskeleton with the plasma membrane, likely through regulating the cholesterol content of lipid rafts.</jats:p> PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts The Journal of Neuroscience |
| doi_str_mv |
10.1523/jneurosci.1908-14.2014 |
| facet_avail |
Online Free |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMTkwOC0xNC4yMDE0 |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMTkwOC0xNC4yMDE0 |
| institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
| imprint |
Society for Neuroscience, 2014 |
| imprint_str_mv |
Society for Neuroscience, 2014 |
| issn |
1529-2401 0270-6474 |
| issn_str_mv |
1529-2401 0270-6474 |
| language |
English |
| mega_collection |
Society for Neuroscience (CrossRef) |
| match_str |
lee2014pmp22iscriticalforactinmediatedcellularfunctionsandforestablishinglipidrafts |
| publishDateSort |
2014 |
| publisher |
Society for Neuroscience |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Neuroscience |
| source_id |
49 |
| title |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_unstemmed |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_full |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_fullStr |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_full_unstemmed |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_short |
PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_sort |
pmp22 is critical for actin-mediated cellular functions and for establishing lipid rafts |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.1908-14.2014 |
| publishDate |
2014 |
| physical |
16140-16152 |
| description |
<jats:p>Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions. Using<jats:italic>in vitro</jats:italic>models, we discovered that, in the absence of PMP22, the migration and adhesion capacity of Schwann cells and fibroblasts are similarly impaired. Furthermore, PMP22-deficient Schwann cells produce shortened myelin internodes, and display compressed axial cell length and collapsed lamellipodia. During early postnatal development, F-actin-enriched Schmidt-Lanterman incisures do not form properly in nerves from PMP22<jats:sup>−/−</jats:sup>mice, and the expression and localization of molecules associated with uncompacted myelin domains and lipid rafts, including flotillin-1, cholesterol, and GM1 ganglioside, are altered. In addition, we identified changes in the levels and distribution of cholesterol and ApoE when PMP22 is absent. Significantly, cholesterol supplementation of the culture medium corrects the elongation and migration deficits of PMP22<jats:sup>−/−</jats:sup>Schwann cells, suggesting that the observed functional impairments are directly linked with cholesterol deficiency of the plasma membrane. Our findings support a novel role for PMP22 in the linkage of the actin cytoskeleton with the plasma membrane, likely through regulating the cholesterol content of lipid rafts.</jats:p> |
| container_issue |
48 |
| container_start_page |
16140 |
| container_title |
The Journal of Neuroscience |
| container_volume |
34 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792341776430792718 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:24:35.81Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=PMP22+Is+Critical+for+Actin-Mediated+Cellular+Functions+and+for+Establishing+Lipid+Rafts&rft.date=2014-11-26&genre=article&issn=1529-2401&volume=34&issue=48&spage=16140&epage=16152&pages=16140-16152&jtitle=The+Journal+of+Neuroscience&atitle=PMP22+Is+Critical+for+Actin-Mediated+Cellular+Functions+and+for+Establishing+Lipid+Rafts&aulast=Notterpek&aufirst=Lucia&rft_id=info%3Adoi%2F10.1523%2Fjneurosci.1908-14.2014&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792341776430792718 |
| author | Lee, Sooyeon, Amici, Stephanie, Tavori, Hagai, Zeng, Waylon M., Freeland, Steven, Fazio, Sergio, Notterpek, Lucia |
| author_facet | Lee, Sooyeon, Amici, Stephanie, Tavori, Hagai, Zeng, Waylon M., Freeland, Steven, Fazio, Sergio, Notterpek, Lucia, Lee, Sooyeon, Amici, Stephanie, Tavori, Hagai, Zeng, Waylon M., Freeland, Steven, Fazio, Sergio, Notterpek, Lucia |
| author_sort | lee, sooyeon |
| container_issue | 48 |
| container_start_page | 16140 |
| container_title | The Journal of Neuroscience |
| container_volume | 34 |
| description | <jats:p>Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions. Using<jats:italic>in vitro</jats:italic>models, we discovered that, in the absence of PMP22, the migration and adhesion capacity of Schwann cells and fibroblasts are similarly impaired. Furthermore, PMP22-deficient Schwann cells produce shortened myelin internodes, and display compressed axial cell length and collapsed lamellipodia. During early postnatal development, F-actin-enriched Schmidt-Lanterman incisures do not form properly in nerves from PMP22<jats:sup>−/−</jats:sup>mice, and the expression and localization of molecules associated with uncompacted myelin domains and lipid rafts, including flotillin-1, cholesterol, and GM1 ganglioside, are altered. In addition, we identified changes in the levels and distribution of cholesterol and ApoE when PMP22 is absent. Significantly, cholesterol supplementation of the culture medium corrects the elongation and migration deficits of PMP22<jats:sup>−/−</jats:sup>Schwann cells, suggesting that the observed functional impairments are directly linked with cholesterol deficiency of the plasma membrane. Our findings support a novel role for PMP22 in the linkage of the actin cytoskeleton with the plasma membrane, likely through regulating the cholesterol content of lipid rafts.</jats:p> |
| doi_str_mv | 10.1523/jneurosci.1908-14.2014 |
| facet_avail | Online, Free |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTUyMy9qbmV1cm9zY2kuMTkwOC0xNC4yMDE0 |
| imprint | Society for Neuroscience, 2014 |
| imprint_str_mv | Society for Neuroscience, 2014 |
| institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
| issn | 1529-2401, 0270-6474 |
| issn_str_mv | 1529-2401, 0270-6474 |
| language | English |
| last_indexed | 2024-03-01T16:24:35.81Z |
| match_str | lee2014pmp22iscriticalforactinmediatedcellularfunctionsandforestablishinglipidrafts |
| mega_collection | Society for Neuroscience (CrossRef) |
| physical | 16140-16152 |
| publishDate | 2014 |
| publishDateSort | 2014 |
| publisher | Society for Neuroscience |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Neuroscience |
| source_id | 49 |
| spelling | Lee, Sooyeon Amici, Stephanie Tavori, Hagai Zeng, Waylon M. Freeland, Steven Fazio, Sergio Notterpek, Lucia 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1908-14.2014 <jats:p>Haploinsufficiency of peripheral myelin protein 22 (PMP22) causes hereditary neuropathy with liability to pressure palsies, a peripheral nerve lesion induced by minimal trauma or compression. As PMP22 is localized to cholesterol-enriched membrane domains that are closely linked with the underlying actin network, we asked whether the myelin instability associated with PMP22 deficiency could be mediated by involvement of the protein in actin-dependent cellular functions and/or lipid raft integrity. In peripheral nerves and cells from mice with PMP22 deletion, we assessed the organization of filamentous actin (F-actin), and actin-dependent cellular functions. Using<jats:italic>in vitro</jats:italic>models, we discovered that, in the absence of PMP22, the migration and adhesion capacity of Schwann cells and fibroblasts are similarly impaired. Furthermore, PMP22-deficient Schwann cells produce shortened myelin internodes, and display compressed axial cell length and collapsed lamellipodia. During early postnatal development, F-actin-enriched Schmidt-Lanterman incisures do not form properly in nerves from PMP22<jats:sup>−/−</jats:sup>mice, and the expression and localization of molecules associated with uncompacted myelin domains and lipid rafts, including flotillin-1, cholesterol, and GM1 ganglioside, are altered. In addition, we identified changes in the levels and distribution of cholesterol and ApoE when PMP22 is absent. Significantly, cholesterol supplementation of the culture medium corrects the elongation and migration deficits of PMP22<jats:sup>−/−</jats:sup>Schwann cells, suggesting that the observed functional impairments are directly linked with cholesterol deficiency of the plasma membrane. Our findings support a novel role for PMP22 in the linkage of the actin cytoskeleton with the plasma membrane, likely through regulating the cholesterol content of lipid rafts.</jats:p> PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts The Journal of Neuroscience |
| spellingShingle | Lee, Sooyeon, Amici, Stephanie, Tavori, Hagai, Zeng, Waylon M., Freeland, Steven, Fazio, Sergio, Notterpek, Lucia, The Journal of Neuroscience, PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts, General Neuroscience |
| title | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_full | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_fullStr | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_full_unstemmed | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_short | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| title_sort | pmp22 is critical for actin-mediated cellular functions and for establishing lipid rafts |
| title_unstemmed | PMP22 Is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.1908-14.2014 |