Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1
- 1Harvard Medical School
Abstract
Integrin 3{beta}1 (ITG3{beta}1) is a member of an integrin subfamily that binds to laminin proteins and promotes attachment of epithelial cells to the basement membrane. ITG3{beta}1 forms a complex with the tetraspanin CD151, and loss-of-function mutations in both ITG3 and CD151 cause epidermolysis bullosa, a severe skin blistering disease resulting from a defect in basement membrane attachment. Here, we report the cryoEM structure of an ITG3{beta}1 complex with CD151 and show that mutation of CD151 at the binding interface disrupts complex formation in cells. Strikingly, CRISPR-mediated knockout of CD151 leads to a variably penetrant ITG3{beta}1 surface export defect that is restored by re-expression of wild-type but not interface-mutated CD151. Together, these studies define the molecular basis for binding of CD151 to ITG3{beta}1, and show that CD151 promotes ITG3{beta}1 surface export, providing a biochemical explanation for the CD151 loss-of-function phenotype in epidermolysis bullosa.
Related
- Activation of α7 Nicotinic Acetylcholine Receptor Inhibits Neutrophil ex vivo Swarming and Pulmonary Recruitment in Inflamed Mice through an Integrin αMβ2-dependent Mechanism
- Context-dependent roles of integrin CD11d in neutrophil responses during sepsis
- Integrin-dependent neutrophil slowing reduces lung perfusion and supports metastasis in a model of breast cancer
- Tetraspanin changes in septic blood are organized by cell type, with monocyte CD82 induction and leukocyte CD37 loss associated with mortality
- Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions
BibTeX
@misc{litzau2026structural,
title = {{Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1}},
author = {L. Litzau and E. Wren and A. C. Kruse and S. C. Blacklow},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748654},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748654v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Structural basis for tetraspanin-dependent surface export and adhesive function of integrin α3β1
AU - L. Litzau
AU - E. Wren
AU - A. C. Kruse
AU - S. C. Blacklow
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748654
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748654v1
AB - Integrin 3{beta}1 (ITG3{beta}1) is a member of an integrin subfamily that binds to laminin proteins and promotes attachment of epithelial cells to the basement membrane. ITG3{beta}1 forms a complex with the tetraspanin CD151, and loss-of-function mutations in both ITG3 and CD151 cause epidermolysis bullosa, a severe skin blistering disease resulting from a defect in basement membrane attachment. Here, we report the cryoEM structure of an ITG3{beta}1 complex with CD151 and show that mutation of CD151 at the binding interface disrupts complex formation in cells. Strikingly, CRISPR-mediated knockout of CD151 leads to a variably penetrant ITG3{beta}1 surface export defect that is restored by re-expression of wild-type but not interface-mutated CD151. Together, these studies define the molecular basis for binding of CD151 to ITG3{beta}1, and show that CD151 promotes ITG3{beta}1 surface export, providing a biochemical explanation for the CD151 loss-of-function phenotype in epidermolysis bullosa.
ER -