The interplay between G protein-coupled receptor kinase 2 (GRK2) and histone deacetylase 6 (HDAC6) at the crossroads of epithelial cell motility.
G protein-coupled receptor kinase 2 (GRK2) is emerging as a key integrative node in cell migration control. In addition to its canonical role in the desensitization of G protein-coupled receptors involved in chemotaxis, novel recently identified GRK2 substrates and interacting partners appear to mediate the GRK2-dependent modulation of diverse molecular processes involved in motility, such as gradient sensing, cell polarity or cytoskeletal reorganization. We have recently identified an interaction between GRK2 and histone deacetylase 6 (HDAC6), a major cytoplasmic α-tubulin deacetylase involved in cell motility and adhesion. GRK2 dynamically associates with and phosphorylates HDAC6 to stimulate its α-tubulin deacetylase activity at specific cellular localizations such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility. This GRK2-HDAC6 functional interaction may have important implications in pathological contexts related to aberrant epithelial cell migration.
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, Madrid, Spain.
Vanesa
V
Lafarga
Federico
F
Mayor
Petronila
P
Penela
D000107:Acetylation; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D002633:Chemotaxis; D051356:Cortactin / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism
C495868:CTTN protein, human; D051356:Cortactin; D056572:Histone Deacetylase Inhibitors; D014404:Tubulin; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases