In this issue

The nuclear lamina forms a scaffold that lies beneath the inner nuclear membrane (INM). It maintains the shape of the nucleus and the spacing of nuclear pores, as well as playing roles in the organization of heterochromatin and regulation of DNA replication and transcription. In Cell Science at a Glance, Roland Foisner illustrates the arrangement of the nuclear lamina, showing how a filament network of A- and B-type lamins is connected to the INM and integral membrane proteins that reside within it.

Present in all eukaryotes, microtubules are an essential component of the cytoskeleton, and control of their dynamics by microtubule-associated proteins (MAPs) is critical for cell division, cell polarity and morphogenesis. The discovery of a family of MAPs that has representatives in amoebae (DdCP224), yeast (Dis1/Stu2p), plants (MOR1) and animals (XMAP215/Minispindles/TOG) is therefore a significant advance. Hiroyuki Ohkura and colleagues review our understanding of the functions of the only family of MAPs known to be present in animals and plants, which they term the Dis1/TOG family. Dis1/TOG MAPs are microtubule-binding proteins whose mutation leads to microtubule-assembly defects and defective spindle formation. They possess a modular domain structure, containing a variable number of HEAT motifs, which probably allow them to interact with many different molecules (e.g. kinesin-like proteins and D-TACC). Dis1/TOG MAPs might thus function in a variety of cellular processes. Indeed strong evidence supports their involvement in cytoplasmic microtubule assembly, spindle assembly, stabilization of spindle poles, kinetochore function and cell morphogenesis.

Cell polarization and cell migration are essential for processes such as wound healing, tissue remodelling and development. We know much about the roles of actin rearrangements and their regulation by Rho-family GTPases in cell migration. But what part do microtubules play, and how is their contribution regulated? Torsten Wittman and Clare Waterman-Storer discuss evidence for regulation of Rho proteins by microtubules, and vice versa, in migrating cells. Microtubules have been shown to control the polarity of migrating cells. Furthermore, recent work indicates that microtubule dynamics can locally regulate not only lamellipodium extension but also the formation of adhesive contacts and actin stress fibres that occurs during migration. Rho proteins - well-established regulators of actin dynamics - are likely to be involved, since biochemical studies indicate that the assembly state of microtubules can control RhoA and Rac1 activity. Moreover, the reverse is also true. Rho proteins and microtubules might thus be part of a feedback loop that promotes asymmetries in actin contractility and substrate adhesion and, consequently, polarization and directional movement.

Complex I is the classical entry point into the respiratory chain, receiving electrons from NADH on the inner face of the inner mitochondrial membrane (IMM) and transferring them to ubiquinone. Many organisms also possess ‘alternative’ NADH:ubiquinone oxidoreductases, however, which can reside on either face of the IMM, depending on the organism. Stefan Kerscher and co-workers have studied these enzymes in Y. lipolytica - a yeast that has a single-subunit alternative NADH:ubiquinone oxidoreductase (NDH2) on the outer face of the IMM. They show that mutations in complex I are lethal but deletion of NDH2 is not. Significantly, targeting of NDH2 to the inner face of the IMM (so it can receive matrix NADH) rescues complex I deficiency. This indicates that NDH2 requires no additional subunits and can associate with the inner face of the IMM - alternative NADH:ubiquinone oxidoreductases that naturally reside on the inner face (e.g. S. cerevisiae SCND1) could therefore have evolved from NDH2-like enzymes in a single step. The results also show that shuttle mechanisms that transfer NADH out of the matrix across the IMM to NDH2 are insufficient to compensate for complex I deficiency. Furthermore, they establish a yeast model for human mitochondrial disorders caused by mutations in complex I.

The activities of lysosomal cysteine proteases in mammals and plants are regulated by a group of endogenous inhibitors termed cystatins. Cysteine proteases are also present in many lower eukaryotes - in Trypanosoma cruzi, for example, the enzymes are essential during invasion of host cells - but whether lower eukaryotes possess endogenous cysteine protease inhibitors has been unclear. Julio Scharfstein and co-workers now demonstrate that T. cruzi contains a novel cysteine protease inhibitor: chagasin. Chagasin is a tight-binding, reversible inhibitor of palpain-like cysteine proteases and is unrelated to the cystatins. Its expression is developmentally regulated and inversely correlates with expression of the major T. cruzi cysteine protease, cruzipain, which could reflect differential requirements for lysosomal protein catabolism at different stages of the parasite life cycle. The authors also show that both chagasin and cruzipain are present at the cell surface in T. cruzi amastigotes, raising the possibility that the intersection of chagasin and cruzipain trafficking pathways represents a checkpoint for regulation of proteolysis in trypanosomatid protozoa.

In a letter to Caveman, Alpine Cave Dweller reports that his lab is being closed down. Apparently, those evicting him have deemed that centralization and Big Science are the way forward. Caveman offers his sympathies: he agrees that there is not a single recipe for good science and feels that the contributions of individuals can go unrecognized in big groups.