Final Report Summary - NPC GENEXPRESS (The nuclear pore connection: adaptor complexes bridging genome regulation and nuclear transport) Nuclear pore complexes (NPCs) are gatekeepers at the nuclear envelope mediating traffic between the nucleus and cytoplasm. Unlike simpler protein channels that insert into a single lipid bilayer, NPCs are embedded in pores formed by the fusion of the outer and inner nuclear membranes. Beyond transport, evolution has added numerous functions to NPCs, exploiting their unique location and compositional complexity. The NPC basket is appended to the nucleoplasmic side of the NPC core, protruding into the chromatin-filled nuclear space. From this location, the NPC basket interacts with transport and chromatin factors. This impacts on the organization and activity of chromatin, adding new spatial dimensions to gene expression. How interactions between NPC proteins and chromatin modify gene activities is a fundamental question in NPC biology. We could show that NPC proteins employ adaptors to regulate directly the transcription machinery. These findings explain how gene-NPC contacts are converted into defined transcriptional outputs at the molecular level. Highlighting the multifaceted roles of NPCs, we have further discovered a new function for NPC basket proteins in remodeling the nuclear membrane to promote NPC and nuclear envelope integrity. This opens up many new questions concerning the structure-function relationship of the NPC basket with the underlying membrane.
