PUBLICATION
Integrin intra-heterodimer affinity inversely correlates with integrin activatability
- Authors
- Sun, G., Guillon, E., Holley, S.A.
- ID
- ZDB-PUB-210610-7
- Date
- 2021
- Source
- Cell Reports 35: 109230 (Other)
- Registered Authors
- Holley, Scott
- Keywords
- cell adhesion, fibronectin, fluorescence cross-correlation spectroscopy, fluorescence lifetime imaging, fluorescence resonance energy transfer, integrin, intra-heterodimer stability, molecular dynamics, somitogenesis, zebrafish
- MeSH Terms
-
- Animals
- Humans
- Integrins/metabolism*
- Zebrafish
- PubMed
- 34107244 Full text @ Cell Rep.
Citation
Sun, G., Guillon, E., Holley, S.A. (2021) Integrin intra-heterodimer affinity inversely correlates with integrin activatability. Cell Reports. 35:109230.
Abstract
Integrins are heterodimeric cell surface receptors composed of an α and β subunit that mediate cell adhesion to extracellular matrix proteins such as fibronectin. We previously studied integrin α5β1 activation during zebrafish somitogenesis, and in the present study, we characterize the integrin αV fibronectin receptors. Integrins are activated via a conformational change, and we perform single-molecule biophysical measurements of both integrin activation via fluorescence resonance energy transfer (FRET)-fluorescence lifetime imaging microscopy (FLIM) and integrin intra-heterodimer stability via fluorescence cross-correlation spectroscopy (FCCS) in living embryos. We find that integrin heterodimers that exhibit robust cell surface expression, including αVβ3, αVβ5, and αVβ6, are never activated in this in vivo context, even in the presence of fibronectin matrix. In contrast, activatable integrins, such as integrin αVβ1, and alleles of αVβ3, αVβ5, αVβ6 that are biased to the active conformation exhibit poor cell surface expression and have a higher intra-heterodimer dissociation constant (KD). These observations suggest that a weak integrin intra-heterodimer affinity decreases integrin cell surface stability and increases integrin activatability.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping