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Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy
Published on: November 1, 2021
A novel GRK2/HDAC6 interaction modulates cell spreading and motility
Vanesa Lafarga1, Ivette Aymerich, Olga Tapia
1Departamento de Biología Molecular, and Centro de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
The EMBO Journal
|December 24, 2011
Summary
G protein-coupled receptor kinase 2 (GRK2) stimulates HDAC6, enhancing cell motility by deacetylating microtubules. This interaction is crucial for cell migration and spreading, with implications for disease.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Microtubule (MT) acetylation/deacetylation dynamics regulate cell motility and adhesion.
- Histone deacetylase 6 (HDAC6) is a primary cytoplasmic enzyme controlling α-tubulin deacetylation.
Purpose of the Study:
- To identify novel regulators of HDAC6 activity.
- To investigate the role of G protein-coupled receptor kinase 2 (GRK2) in modulating HDAC6 and its impact on cell behavior.
Main Methods:
- Co-immunoprecipitation to assess protein interactions.
- In vitro kinase assays to determine phosphorylation sites.
- Cell migration and spreading assays using mutant GRK2.
- Immunofluorescence microscopy to visualize protein localization and MT acetylation.
Main Results:
- GRK2 directly associates with and phosphorylates HDAC6, enhancing its deacetylase activity.
- GRK2 levels inversely correlate with α-tubulin acetylation.
- GRK2 and HDAC6 colocalize in lamellipodia, promoting cell migration.
- Mutant GRK2 impairs cell migration and protrusive activity due to increased MT acetylation.
Conclusions:
- GRK2 is a novel stimulator of HDAC6, regulating α-tubulin deacetylation and cell motility.
- Phosphorylation of GRK2 at S670 is critical for its stimulatory effect on HDAC6.
- The GRK2/HDAC6 pathway plays a significant role in cell spreading dynamics and may be relevant in pathological conditions.
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