Organelle-Specific, Rapid Induction of Molecular Activities and Membrane Tethering

Using a series of novel chemically-inducible dimerization probes, we generated a system in which proteins were rapidly targeted to individual intracellular organelles. We demonstrated that a Ras GTPase can be activated at distinct intracellular locations and that membranes from two organelles, ER and mitochondria, can be inducibly tethered. Innovative techniques to rapidly perturb molecular activities and organelle-organelle communications at precise locations and timing will provide powerful strategies to dissect spatio-temporally complex biological processes. Keywords chemically-inducible cellular perturbation; dimerization probe; organelle-organelle interaction; small GTPase; signal compartmentalization Signaling events in many cells are local and rapid, and they can compensate certain perturbations to the cell. Therefore, elucidating the structure and function of complex signaling networks requires perturbation which is faster than the signaling events themselves, which acts within precisely defined spatial domains, and which can be applied at desired time points. Based on a rapamycin-driven heterodimerization technique1, we hav