Regulation of cytokinesis

At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis, it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified. This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may regulate it. Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998     

Three-dimensional structure of motor molecules

Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules.     

The pleiotropic functions of aspirin: mechanisms of action

Recent studies have suggested that aspirin and aspirin-like compounds have a variety of actions in addition to their well-studied ability to inhibit cyclooxygenases. These actions include inhibition of the uncoupling of oxidative phosphorylation, decreases in adenosine triphosphate stores, increases in extracellular adenosine, downregulation of the expression and activity of inducible nitric oxide synthetase, inhibition and/or stimulation of various mitogen-activated protein kinase activities and inhibition of nuclear factor binding κB site (NF-κB) activation. Moreover, aspirin-like compounds have recently been shown to have previously unappreciated clinical and biological effects, some apparently independent of cyclooxygenase. In this review we discuss the various mechanisms of action of aspirin-like compounds and their relevance to clinical disease and therapy. Received 1 February 1999; received after revision 1 April 1999; accepted 7 May 1999     

Ventral neural tube cells differentiate into hepatocytes in the chick embryo

A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study show an additional source for the formation of liver cells. Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998     

Roles of postsynaptic density-95/synapse-associated protein 90 and its interacting proteins in the organization of synapses

Synapses are central stages for neurotransmission. Neurotransmitters are released from the presynaptic membrane of one neuron, and bind to the receptors accumulated at the postsynaptic membrane, followed by the activation of the other neuron. The strength of a synapse is modified depending on the history of the previous neurotransmissions. This property is called synaptic plasticity and is implicated in learning and memory. Synapses contain not only the components essential for neurotransmission but also the signalling molecules involved in synaptic plasticity. The elucidation of the molecular structures of synapses is one of the key steps to understand the mechanism of learning and memory. Recent studies have revealed postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 as a core component in the architecture of synapses. In this review, we summarize up-to-date information about PSD-95/SAP90 and its interacting proteins, and the organization of synapses orchestrated     

Are elicitins cryptograms in plant-Oomycete communications?

Stimulation of plant natural defenses is an important challenge in phytoprotection prospects. In that context, elicitins, which are small proteins secreted by Phytophthora and Pythium species, have been shown to induce a hypersensitive-like reaction in tobacco plants. Moreover, these plants become resistant to their pathogens, and thus this interaction constitutes an excellent model to investigate the signaling pathways leading to plant resistance. However, most plants are not reactive to elicitins, although they possess the functional signaling pathways involved in tobacco responses to elicitin. The understanding of factors involved in this reactivity is needed to develop agronomic applications. In this review, it is proposed that elicitins could interact with regulating cell wall proteins before they reach the plasma membrane. Consequently, the plant reactivity or nonreactivity status could result from the equilibrium reached during this interaction. The possibility of overexpressing the elicitins directly from genomic DNA in Pichia pastoris allows site-directed mutagenesis experiments and structure/function studies. The recent discovery of the sterol carrier activity of elicitins brings a new insight on their molecular activity. This constitutes a crucial property, since the formation of a sterol-elicitin complex is required to trigger the biological responses of tobacco cells and plants. Only the elicitins loaded with a sterol are able to bind to their plasmalemma receptor, which is assumed to be an allosteric calcium channel. Moreover, Phytophthora and Pythium do not synthesize the sterols required for their growth and their fructification, and elicitins may act as shuttles trapping the sterols from the host plants. Sequence analysis of elicitin genes from several Phytophthora species sheds unexpected light on the phylogenetic relationships among the genus, and suggests that the expression of elicitins is under tight regulatory control. Finally, general involvement of these lipid transfer proteins in the biology of Pythiaceae, and in plant defense responses, is discussed. A possible scheme for the coevolution between Phytophthora and tobacco plants is approached.     

Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.