Regulation of stress granule dynamics by Grb7 and FAK signalling pathway.
Cells form stress granules (SGs) in response to environmental stresses, which constitute cytoplasmic domains where mRNAs are stored and translation is halted. Although several components are found in SGs, it is poorly understood as to how SGs are formed and dissolved. We identified growth factor receptor-bound protein 7 (Grb7), an RNA-binding, translational regulator, as an integral component of SGs, which directly interacts with Hu antigen R (HuR) and is required for cells to form SGs. When stress is terminated, Grb7 is hyperphosphorylated by focal adhesion kinase (FAK), loses its ability to directly interact with HuR and is dissociated from SG components, thereby disrupting SGs in recovering cells. Consistently, dominant-negative hypophospho mutants of FAK and Grb7 significantly attenuate SG disassembly during recovery. FAK activation followed by its phosphorylating Grb7 constitutes a cell-autonomous signalling pathway that regulates the disassembly of SGs and translational stimulation during recovery. This is the first reported pathway actively regulating the dynamics of SGs.
Tsai
Nien-Pei
NP
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Ho
Ping-Chih
PC
Wei
Li-Na
LN
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000378:metabolism*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051382:GRB7 Adaptor Protein / Q000378:metabolism*; D006358:Hot Temperature; D051379:Mice; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism; D013312:Stress, Physiological
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C495956:Grb7 protein, mouse; D016601:RNA-Binding Proteins; D051382:GRB7 Adaptor Protein; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse