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The desmosome is a mesoscale lipid raft–like membrane domain
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| Zeitschriftentitel: | Molecular Biology of the Cell |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | Molecular Biology of the Cell, 30, 2019, 12, S. 1390-1405 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Cell Biology (ASCB)
|
| Schlagwörter: |
| author_facet |
Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. |
|---|---|
| author |
Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. |
| spellingShingle |
Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. Molecular Biology of the Cell The desmosome is a mesoscale lipid raft–like membrane domain Cell Biology Molecular Biology |
| author_sort |
lewis, joshua d. |
| spelling |
Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. 1059-1524 1939-4586 American Society for Cell Biology (ASCB) Cell Biology Molecular Biology http://dx.doi.org/10.1091/mbc.e18-10-0649 <jats:p>Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.</jats:p> The desmosome is a mesoscale lipid raft–like membrane domain Molecular Biology of the Cell |
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| title |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_unstemmed |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_full |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_fullStr |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_full_unstemmed |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_short |
The desmosome is a mesoscale lipid raft–like membrane domain |
| title_sort |
the desmosome is a mesoscale lipid raft–like membrane domain |
| topic |
Cell Biology Molecular Biology |
| url |
http://dx.doi.org/10.1091/mbc.e18-10-0649 |
| publishDate |
2019 |
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1390-1405 |
| description |
<jats:p>Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.</jats:p> |
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| author | Lewis, Joshua D., Caldara, Amber L., Zimmer, Stephanie E., Stahley, Sara N., Seybold, Anna, Strong, Nicole L., Frangakis, Achilleas S., Levental, Ilya, Wahl, James K., Mattheyses, Alexa L., Sasaki, Takashi, Nakabayashi, Kazuhiko, Hata, Kenichiro, Matsubara, Yoichi, Ishida-Yamamoto, Akemi, Amagai, Masayuki, Kubo, Akiharu, Kowalczyk, Andrew P. |
| author_facet | Lewis, Joshua D., Caldara, Amber L., Zimmer, Stephanie E., Stahley, Sara N., Seybold, Anna, Strong, Nicole L., Frangakis, Achilleas S., Levental, Ilya, Wahl, James K., Mattheyses, Alexa L., Sasaki, Takashi, Nakabayashi, Kazuhiko, Hata, Kenichiro, Matsubara, Yoichi, Ishida-Yamamoto, Akemi, Amagai, Masayuki, Kubo, Akiharu, Kowalczyk, Andrew P., Lewis, Joshua D., Caldara, Amber L., Zimmer, Stephanie E., Stahley, Sara N., Seybold, Anna, Strong, Nicole L., Frangakis, Achilleas S., Levental, Ilya, Wahl, James K., Mattheyses, Alexa L., Sasaki, Takashi, Nakabayashi, Kazuhiko, Hata, Kenichiro, Matsubara, Yoichi, Ishida-Yamamoto, Akemi, Amagai, Masayuki, Kubo, Akiharu, Kowalczyk, Andrew P. |
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| description | <jats:p>Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.</jats:p> |
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| spelling | Lewis, Joshua D. Caldara, Amber L. Zimmer, Stephanie E. Stahley, Sara N. Seybold, Anna Strong, Nicole L. Frangakis, Achilleas S. Levental, Ilya Wahl, James K. Mattheyses, Alexa L. Sasaki, Takashi Nakabayashi, Kazuhiko Hata, Kenichiro Matsubara, Yoichi Ishida-Yamamoto, Akemi Amagai, Masayuki Kubo, Akiharu Kowalczyk, Andrew P. 1059-1524 1939-4586 American Society for Cell Biology (ASCB) Cell Biology Molecular Biology http://dx.doi.org/10.1091/mbc.e18-10-0649 <jats:p>Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.</jats:p> The desmosome is a mesoscale lipid raft–like membrane domain Molecular Biology of the Cell |
| spellingShingle | Lewis, Joshua D., Caldara, Amber L., Zimmer, Stephanie E., Stahley, Sara N., Seybold, Anna, Strong, Nicole L., Frangakis, Achilleas S., Levental, Ilya, Wahl, James K., Mattheyses, Alexa L., Sasaki, Takashi, Nakabayashi, Kazuhiko, Hata, Kenichiro, Matsubara, Yoichi, Ishida-Yamamoto, Akemi, Amagai, Masayuki, Kubo, Akiharu, Kowalczyk, Andrew P., Molecular Biology of the Cell, The desmosome is a mesoscale lipid raft–like membrane domain, Cell Biology, Molecular Biology |
| title | The desmosome is a mesoscale lipid raft–like membrane domain |
| title_full | The desmosome is a mesoscale lipid raft–like membrane domain |
| title_fullStr | The desmosome is a mesoscale lipid raft–like membrane domain |
| title_full_unstemmed | The desmosome is a mesoscale lipid raft–like membrane domain |
| title_short | The desmosome is a mesoscale lipid raft–like membrane domain |
| title_sort | the desmosome is a mesoscale lipid raft–like membrane domain |
| title_unstemmed | The desmosome is a mesoscale lipid raft–like membrane domain |
| topic | Cell Biology, Molecular Biology |
| url | http://dx.doi.org/10.1091/mbc.e18-10-0649 |