The desmosome is a mesoscale lipid raft–like membrane domain

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Bibliographische Detailangaben
Zeitschriftentitel:	Molecular Biology of the Cell
Personen und Körperschaften:	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.
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:	Cell Biology Molecular Biology

Details
Zusammenfassung:	<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>
Umfang:	1390-1405
ISSN:	1939-4586 1059-1524
DOI:	10.1091/mbc.e18-10-0649