The mechanism of crm1-mediated nuclear export

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Project objective

Research objectives and content The CRM1 protein is an export receptor for leucine-rich nuclear export signals (NESs). It was shown to mediate rapid transport of proteins and RNAs from the nucleus to the cytoplasm. Association of CRM1 with NESs is only stable in the presence of the nuclear form of the GTPase Ran, suggesting that hydrolysis of the Ran-bound GTP causes the export complexes to fall apart in the cytoplasm. Our aim is to test this hypothesis, and to obtain a detailed understanding of the mechanism of CRM1/NES binding to and release. For this purpose I will use in vitro assays with recombinant components to mimick nuclear or cytoplasmic binding conditions. NES-containing (ribonuclear) proteins are exported via the nuclear pore complex, however, nothing is known about the exact mechanism of this process. By manipulating the NES-bound state of CRM1 I will study export-specific interactions with NPC-components. I also propose to study the energy requirements for CRM1-mediated export making use of an in vitro export system. Training content (objective, benefit and expected impact) For these studies I will profit from the long expertise of the host laboratory in the field of nucleocytoplasmic transport. The use of an in vitro nuclear export system that was developed in Dr.Mattaj's lab will be particularly valuable. Links with industry / industrial relevance (22)

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Participants

• EUROPEAN MOLECULAR BIOLOGY LABORATORY · HEIDELBERGCoordinatorGermany

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