CTP:phosphocholine cytidylyltransferase: insights into regulatory mechanisms and novel functions

A key regulatory enzyme in phosphatidylcholine biosynthesis, CTP:cholinephosphate cytidylyltransferase (CCT), catalyzes the formation of CDP-choline. This review discusses the essential features of CCT and addresses intriguing new insights into the catalytic and regulatory properties of this complex enzyme. Characterization of a lipid-binding segment in rat CCT is described and the role of lipids in CCT activation is discussed. An analysis of the phosphorylation domain is presented and possible physiological rationales for reversible phosphorylation of CCT are discussed. The nuclear localization of CCT is examined in the context of multiple CCT isoforms, as is recent evidence establishing a potential link between CCT activity and vesicular transport.     

Plant meristems: a merry-go-round of signals

Recent studies have provided significant new insights into the gene actions that specify and maintain stem cells in plant shoots and roots. New layers of genetic control and potential signalling pathways and effector mechanisms have emerged from these new studies and will be reviewed here. These new findings refine the current model in which stem cells in plant meristems are regulated by negative feedback loops and uncover a fundamental mechanism for stem cell maintenance that might be common to shoots and roots.     

Plant meristems: the interplay of KNOX and gibberellins

KNOX proteins are required for meristem activity in plants. Recent studies have identified potential targets of KNOX proteins, and in doing so suggested a possible mechanism for the generation of different leaf morphologies.     

Plant meristems: cytokinins--the alpha and omega of the meristem

Recent studies have revealed important new details of how cytokinin-dependent mechanisms control plant growth. Intriguingly, cytokinins are involved in both maintaining meristems and promoting differentiation.     

Plant Aurora kinases play a role in maintenance of primary meristems and control of endoreduplication

? The conserved family of Aurora kinases has multiple functions during mitosis. The roles of plant Aurora kinases have been characterized using inhibitor treatments. ? We down-regulated Aurora kinases in Arabidopsis thaliana using RNA interference (RNAi). We carried out a detailed phenotypic analysis of Aurora RNAi plants, biochemical and microscopic studies of AtAurora1 kinase together with AtTPX2 (targeting protein for Xklp2) and γ-tubulin. ? Cell division defects were observed in plants with reduced expression of Aurora kinases. Furthermore, the maintenance of primary meristems was compromised and RNAi seedlings entered endoreduplication prematurely. AtAurora1, its activator AtTPX2, and γ-tubulin were associated with microtubules in vitro; they were attached to regrowing kinetochore microtubules and colocalized on spindle microtubules and with a subset of early phragmoplast microtubules. Only the AtAurora1 kinase was translocated to the area of the cell plate. ? RNAi silencing of Aurora kinases showed that, in addition to their function in regulating mitosis, the kinases are required for maintaining meristematic activity and controlling the switch from meristematic cell proliferation to differentiation and endoreduplication. The colocalization and co-fractionation of AtAurora1 with AtTPX2, and γ-tubulin on microtubules in a cell cycle-specific manner suggests that AtAurora1 kinase may function to phosphorylate substrates that are critical to the spatiotemporal regulation of acentrosomal microtubule formation and organization.     

Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development

The atrioventricular heart valve leaflets and chordae tendineae are composed of diverse cell lineages and highly organized extracellular matrices that share characteristics with cartilage and tendon cell types in the limb buds and somites. During embryonic chicken valvulogenesis, aggrecan and sox9, characteristic of cartilage cells, are observed in the AV valve leaflets, in contrast to tendon-associated genes scleraxis and tenascin, present in the chordae tendineae. In the limb buds and somites, cartilage cell lineage differentiation is regulated by BMP2, while FGF4 controls tendon cell fate. The ability of BMP2 and FGF4 to induce similar patterns of gene expression in heart valve precursor cells was examined. In multiple assays of cells from prefused endocardial cushions, BMP2 is sufficient to activate Smad1/5/8 phosphorylation and induce sox9 and aggrecan expression, while FGF4 treatment increases phosphorylated MAPK (dpERK) signaling and promotes expression of scleraxis and tenascin. However, these treatments do not alter differentiated lineage gene expression in valve progenitors from fused cushions of older embryos. Together, these studies define regulatory pathways of AV valve progenitor cell diversification into leaflets and chordae tendineae that share inductive interactions and differentiation phenotypes with cartilage and tendon cell lineages.     

Plant meristems: the fiendish SU DOKU of stem-cell maintenance

Three recent studies have uncovered effector mechanisms and novel pathways in the regulation of the dynamic changes to cell behaviour that occur in plant meristems. The results show how exquisite regulation of cell-cycle mechanisms is central to root stem cell homeostasis.     

Neuronal plasticity and cellular immunity: shared molecular mechanisms

It is becoming evident that neurons express an unusual number of molecules that were originally thought to be specific to immune functions. One such molecule, class I major histocompatibility complex, is required in the activity-dependent refinement and plasticity of connections in the developing and adult central nervous system, demonstrating that molecules can perform critical roles in both systems. Recent studies reveal striking parallels between cellular signaling mechanisms in the immune and nervous systems that may provide unexpected insights into the development, function, and diseases of both systems.     

DNA and RNA ligases: structural variations and shared mechanisms

DNA and RNA ligases join 3' OH and 5' PO4 ends in polynucleotide substrates using a three-step reaction mechanism that involves covalent modification of both the ligase enzyme and the polynucleotide substrate with AMP. In the past three years, several polynucleotide ligases have been crystallized in complex with nucleic acid, providing the introductory views of ligase enzymes engaging their substrates. Crystal structures for two ATP-dependent DNA ligases, an NAD+-dependent DNA ligase, and an ATP-dependent RNA ligase demonstrate how ligases utilize the AMP group and their multi-domain architectures to manipulate nucleic acid structure and catalyze the end-joining reaction. Together with unliganded crystal structures of DNA and RNA ligases, a more comprehensive and dynamic understanding of the multi-step ligation reaction mechanism has emerged.     

Memory and addiction: shared neural circuitry and molecular mechanisms

An important conceptual advance in the past decade has been the understanding that the process of drug addiction shares striking commonalities with neural plasticity associated with natural reward learning and memory. Basic mechanisms involving dopamine, glutamate, and their intracellular and genomic targets have been the focus of attention in this research area. These two neurotransmitter systems, widely distributed in many regions of cortex, limbic system, and basal ganglia, appear to play a key integrative role in motivation, learning, and memory, thus modulating adaptive behavior. However, many drugs of abuse exert their primary effects precisely on these pathways and are able to induce enduring cellular alterations in motivational networks, thus leading to maladaptive behaviors. Current theories and research on this topic are reviewed from an integrative systems perspective, with special emphasis on cellular, molecular, and behavioral aspects of dopamine D-1 and glutamate NMDA signaling, instrumental learning, and drug cue conditioning.     

Plant stem cells and their regulations in shoot apical meristems

Stem cells in plants, established during embryogenesis, are located in the centers of the shoot apical meristem (SAM) and the root apical meristem (RAM). Stem cells in SAM have a capacity to renew themselves and to produce new organs and tissues indefinitely. Although fully differentiated organs such as leaves do not contain stem cells, cells in such organs do have the capacity to re-establish new stem cells, especially under the induction of phytohormones in vitro. Cytokinin and auxin are critical in creating position signals in the SAM to maintain the stem cell organizing center and to position the new organ primordia, respectively. This review addresses the distinct features of plant stem cells and focuses on how stem cell renewal and differentiation are regulated in SAMs.     

Nuclear positioning: mechanisms and functions

The nucleus is the largest organelle in the cell and its position is dynamically controlled in space and time, although the functional significance of this dynamic regulation is not always clear. Nuclear movements are mediated by the cytoskeleton which transmits pushing or pulling forces onto the nuclear envelope. Recent studies have shed light on the mechanisms regulating nuclear positioning inside the cell. While microtubules have been known for a long time to be key players in nuclear positioning, the actin and cytoplasmic intermediate filament cytoskeletons have been implicated in this function more recently and various molecular links between the nuclear envelope and cytoplasmic elements have been identified. In this review, we summarize the recent advances in our understanding of the molecular mechanisms involved in the regulation of nuclear localization in various animal cells and give an overview of the evidence suggesting a crucial role of nuclear positioning in cell polarity and physiology and the consequences of nuclear mispositioning in human pathologies.