Export nucléaire des protéines et homéostasie cellulaire Nuclear export of proteins: molecular mechanisms and functions

Résumé

L’apparition du noyau dans les cellules eucaryotes a imposé la mise en place de mécanismes spécifiques permettant d’utiliser et de protéger l’information génétique mais également de coordonner les fonctions nucléaires et cytoplasmiques. Les études menées au cours des 10 dernières années ont permis d’élaborer un modèle selon lequel les molécules importées vers le noyau ou exportées vers le cytoplasme présentent des séquences d’adressage reconnues par des récepteurs spécifiques de transport nucléaire. Ces interactions sont orchestrées par la petite GTPase Ran qui assure la directionnalité des échanges nucléocytoplasmiques. Cet article tentera de faire le point des connaissances sur les mécanismes d’export nucléaire des protéines et le rôle de ces voies de transport dans la régulation d’autres fonctions cellulaires.

Summary

The nucleus of eukaryotic cells spatially separates DNA replication and RNA transcription from cytoplasmic protein synthesis. Thus, the nuclear membrane must ensure a strict and selective molecular control of exchanges between the nucleus and the rest of the cell, not only to protect and correctly transmit genetic information but also to synchronize nuclear and cytoplasmic functions. Studies over the past ten years led to the identification of targeting sequences (nuclear import or export sequences) recognized by specific receptors, called importins and exportins, which induce transport through the nuclear pore complex. Cargo-receptor interactions are orchestrated by Ran, a small and abundant GTPase. The compartmentalization of the factors that control the GDP- and GTP-bound state of Ran is believed to create a steep gradient of RanGDP (cytoplasmic) / RanGTP (nuclear) concentrations across the nuclear membrane. This gradient controls the directionality of nucleocytoplasmic transport pathways since cargo-importin complexes are induced to disassemble upon binding to RanGTP in the nucleus whereas RanGTP is used to assemble cargo-exportin complexes. In this review, we focus on what is known about the various steps involved in nuclear export of proteins, an intracellular route discovered more than 40 years ago, which has remained largely uncharacterized until recently. Furthermore, the regulation of nuclear transport is now considered one of the most efficient mechanisms to adapt cellular responses to environment conditions by restricting access to nuclear or cytoplasmic compartments. In particular, we illustrate here how nuclear export regulation participates to the control of transcriptional responses, cell cycle progression or the establishment of cell polarity.