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The interaction of Gα13 with integrin β1 mediates cell migration by dynamic regulation of RhoA
- Source :
- Molecular Biology of the Cell
- Publication Year :
- 2015
- Publisher :
- American Society for Cell Biology (ASCB), 2015.
-
Abstract
- Gα13 directly binds to the cytoplasmic-domain ExE motif of the integrin β1 subunit. Gα13–β1 interaction mediates β1 integrin–dependent Src activation and transient RhoA inhibition after adhesion. This binding is critical for cell migration on β1 integrin ligands.<br />Heterotrimeric G protein Gα13 is known to transmit G protein–coupled receptor (GPCR) signals leading to activation of RhoA and plays a role in cell migration. The mechanism underlying the role of Gα13 in cell migration, however, remains unclear. Recently we found that Gα13 interacts with the cytoplasmic domain of integrin β3 subunits in platelets via a conserved ExE motif. Here we show that a similar direct interaction between Gα13 and the cytoplasmic domain of the integrin β1 subunit plays a critical role in β1-dependent cell migration. Point mutation of either glutamic acid in the Gα13-binding 767EKE motif in β1 or treatment with a peptide derived from the Gα13-binding sequence of β1 abolished Gα13–β1 interaction and inhibited β1 integrin–dependent cell spreading and migration. We further show that the Gα13-β1 interaction mediates β1 integrin–dependent Src activation and transient RhoA inhibition during initial cell adhesion, which is in contrast to the role of Gα13 in mediating GPCR-dependent RhoA activation. These data indicate that Gα13 plays dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via an integrin signaling pathway. This dynamic regulation of RhoA activity is critical for cell migration on β1 integrin ligands.
- Subjects :
- RHOA
Cell Culture Techniques
CHO Cells
Bioinformatics
GTP-Binding Protein alpha Subunits, G12-G13
CD49c
03 medical and health sciences
Cricetulus
0302 clinical medicine
Cell Movement
Heterotrimeric G protein
Cell Adhesion
Animals
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Molecular Biology
030304 developmental biology
G protein-coupled receptor
Integrin Signaling Pathway
0303 health sciences
biology
Integrin beta1
Cell migration
Articles
Cell Biology
Signaling
Cell biology
HEK293 Cells
biology.protein
Signal transduction
rhoA GTP-Binding Protein
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....79bbc1f530846bc8d2005cf28824c53c