Imaging the translocations of CLIC4 and Epac1

Ponsioen, B.

Cells respond to extracellular cues via receptor signaling. In this manner, cellular behavior is under strict control of hormones, growth factors or neurotransmitters. Binding of a ligand to its cognate receptor triggers a cascade of intracellular signaling events leading to, for instance, activation of transcription factors, regulation of metabolic processes or changes in cell morphology. To regulate such __organized complexity__, molecular interactions in the cell are specific and regulated. Furthermore, these signaling pathways are strictly compartmentalized. This means that spatial restriction facilitates the coupling of a signaling component to its effectors, while it leaves other signaling compartments unaffected. Thus, compartmentalization adds to the specificity of signaling cascades. Signaling complexes are dynamically regulated, i.e. they can be assembled in response to extracellular signals. The dynamic targeting of a signaling molecule to a specialized compartment...Show moreCells respond to extracellular cues via receptor signaling. In this manner, cellular behavior is under strict control of hormones, growth factors or neurotransmitters. Binding of a ligand to its cognate receptor triggers a cascade of intracellular signaling events leading to, for instance, activation of transcription factors, regulation of metabolic processes or changes in cell morphology. To regulate such __organized complexity__, molecular interactions in the cell are specific and regulated. Furthermore, these signaling pathways are strictly compartmentalized. This means that spatial restriction facilitates the coupling of a signaling component to its effectors, while it leaves other signaling compartments unaffected. Thus, compartmentalization adds to the specificity of signaling cascades. Signaling complexes are dynamically regulated, i.e. they can be assembled in response to extracellular signals. The dynamic targeting of a signaling molecule to a specialized compartment becomes manifest as a stimulus-induced translocation. In this thesis, we revealed and studied the translocations of two proteins: those of chloride intracellular channel 4 (CLIC4) and exchange protein directly activated by cAMP 1 (Epac1). Central in these studies were the microscopical techniques that allowed visualization of these translocations with maximal spatiotemporal resolution, most prominently via confocal imaging and measurement of FRET.Show less

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Imaging the translocations of CLIC4 and Epac1