The desmosome is a mesoscale lipid raft-like membrane domain.

Abstract:

: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.

journal_name

Mol Biol Cell

authors

Lewis JD,Caldara AL,Zimmer SE,Stahley SN,Seybold A,Strong NL,Frangakis AS,Levental I,Wahl JK 3rd,Mattheyses AL,Sasaki T,Nakabayashi K,Hata K,Matsubara Y,Ishida-Yamamoto A,Amagai M,Kubo A,Kowalczyk AP

doi

10.1091/mbc.E18-10-0649

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1390-1405

issue

12

eissn

1059-1524

issn

1939-4586

journal_volume

30

pub_type

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