Nuclear Transport The Bottom Line

(Rout et al., J. Cell Biol. 148, 635–651, 2000). The yeast Nucleocytoplasmic transport plays a pivotal role in eunuclear pore is compared and contrasted to the larger karyotic cell function and is relevant to many areas of and more complex vertebrate nuclear pore in the next cell biology. As such, it is somewhat surprising that chapter by Fahrenkrog and Aebi. This chapter puts books on this subject are in short supply. Nuclear Transgreater emphasis on structural methods, including report, edited by Karsten Weis, is a welcome addition. cent work involving cryo-electron tomography and To understand the organization of the book, a brief atomic force microscopy, techniques which are hoped overview of nuclear transport is helpful. Nuclear localizawill improve our understanding of the three-dimensional tion signals (NLSs) and nuclear export signals (NESs) architecture of the nuclear pore. direct proteins to enter or leave the nucleus. Most types Also included in the review by Rout is his model for of nuclear transport use a set of cytoplasmic receptors transport, which is presented in a measured and interderived from a single family of proteins, the importin esting way. Missing from the book, however, is a rendi(or karyopherin ) nuclear transport receptor family. tion of a competing model for the mechanism of transloThese receptors are regulated by the binding of a small cation by Ribbeck and Görlich, EMBO J. 20, 1320–1330, GTPase, Ran. Ran exists predominantly in its GTP form 2001). It should be noted that, although each of the inside the nucleus (where its GDP-GTP exchange factor, models has its strong points, experimental proof of such RCC1, resides), and in its GDP form in the cytoplasm models is hard to come by. Indeed, it has been very (where its GTPase activating protein, RanGAP, is found). difficult to confirm a specific translocation mechanism This nuclear/cytoplasmic RanGTP gradient was recently for the nuclear pore, which contains multiples of 30–50 confirmed visually using novel fluorescent biosensors different proteins in the final 500–1000 protein nuclear (Kalab et al., Science 295, 2452–2456, 2002). pore complex. Getting back to the basics of nuclear transport, an In the third chapter of Nuclear Transport, Bischoff et eager import receptor arrives in the nucleus carrying its al. focus on the small GTPase Ran, a molecule that is cargo and is then approached by RanGTP. The import appropriately crowned the “king” of nuclear transport receptor binds to RanGTP, which causes the receptor to elsewhere in the book. This review provides a wealth of undergo a conformational change and release its cargo, structural and biochemical information on the function completing import. Export receptors show the opposite and regulation of Ran. behavior. They strongly bind to their export cargo (for Four chapters describe different export receptors and example, a nuclear protein containing an NES) only when pathways. In the first of these, Fornerod and Ohno focus simultaneously bound to RanGTP. The heterotrimeric on the receptor that mediates the export of NES-bearing complex of export receptor/RanGTP/NES-bearing pronuclear proteins and certain ribonucleoprotein comtein translocates through the nuclear pore, a structure plexes, exportin 1 or Crm1. This accessible chapter not 400 times the size of the export complex. Immediately only provides a review of the subject and some of the upon reaching the opposite side of the pore, the export historical background leading to the discovery of excomplex dissociates due to the RanGAP tethered to the portins, but also discusses general principles relevant cytoplasmic filaments of the pore. to other types of transport receptors. Simos et al. review Individual organisms contain at least 10–20 members all aspects of exportin-t, a -like receptor that is unique of the importin receptor family. Some are import recepin that it directly recognizes an RNA molecule, i.e., tRNA, tors, specialized for ferrying different nuclear proteins and exports it to the cytoplasm. Izaurralde next deor snRNP cargo into the nucleus. Other receptors are scribes the exciting developments in the area of mRNA specific for exporting nuclear proteins, 5S RNA, tRNA, export. Particularly informative to these reviewers was or ribosomal subunit precursors to the cytoplasm. Ala final export review by Cullen, detailing the lessons