Research

Regulation of Activin/Nodal Signaling by Rap2-Directed Receptor Trafficking (2008.7.7)

TGFβ ligands belonging to the Activin/Nodal family, induces mesoderm and endoderm, specifies the embryonic axes, promotes gastrulation movements, maintains pluripotency of embryonic stem cells, and determines left-right asymmetry in vertebrates. Activin/Nodal ligands signal through type I and type II transmembrane serine/threonine kinase receptors. Ligand binding induces the formation of heteromeric receptor complexes in which type II receptors phosphorylate and activate type I receptors. The activated type I receptors transduce the signal inside the cell through the phosphorylation of the receptor-regulated Smads (R-Smads), Smads 2, and/or Smad3. Once activated, RSmads form complexes with common mediator-Smad (co-Smad), Smad4, and translocate into the nucleus, where they regulate gene expression with DNA-binding partners and transcriptional cofactors both positively and negatively. The strength of Activin/Nodal signaling is represented by the levels of active nuclear Smad2, which are regulated at several steps in signaling cascade. Differential occupancy of receptor leads to varying levels of activated Smad2, and induces different sets of target genes. A recent study demonstrated that the length of time, for which the Activin-Activin receptor signaling complex dwells in the endocytic pathway, determines the duration of the serine/threonine kinase activity of receptor, thereby controlling the intracellular concentration of active Smad2. In fact, endocytosis occurred through the clathrin-dependent endocytic route is required for promotion of Smad-dependent signaling activation. Alternatively, internalization via the lipid-raft/caveolar compartments leads to the accelerated receptor degradation which is mediated by Smad7/Smurf2 complex. Thus, proper partitioning of receptors into two distinct compartments may be essential for the fine control of receptor availability and signaling activity. However, the molecular mechanism underlying this segregation remains unknown. In this study, we showed that Rap2, a member of Ras GTPase family, regulates the trafficking of Activin/Nodal receptors to modulate signaling activity. Rap2 was required for sorting of internalized Activin/Nodal receptors into recycling pathway in the absence of ligand activation and thus maintaining their proper levels at the cell surface. Ligand-activated receptors were not recycled to the plasma membrane, but their turnover was delayed by Rap2. Interestingly, Rap2 counteracted Smad7 function in these processes. We also found that there is difference in the efficiency of Activin/Nodal receptor recycling between dorsal and ventral halves of early embryo, which is regulated by the temporally dynamic expression of Rap2. This led to the differential onset of Smad2 phosphorylation across the dorsoventral axis of Xenopus early embryo. Therefore, our data identify Rap2 as a key player in the regulation of receptor trafficking that might affect cell responsiveness to extracellular ligands and signaling duration. Professor Jin-Kwan Han Department of Life Science Tel: +82-54-279-2126 Fax: +82-54-279-2199 E-mail: jkh@postech.ac.kr

Consciousness versus Unconsciousness: Standard for Partition (2008.12.2)

The way to prevent intra-operative awareness has been paved by joint efforts of medical science and physics. Intra-operative awareness, familiarized through some thriller movies, is a unique physiological phenomenon which causes the patient under general anesthesia to recover consciousness during surgery. The patient experiencing intra-operative awareness may feel the pain or pressure of surgery, hear conversations, or feel as if he cannot breathe, but may be unable to communicate any distress because he has been given a paralytic or muscle relaxant. Professor Seunghwan Kim (Department of Physics), in a joint research with Doctor UnCheol Lee of University of Michigan, who is a POSTECH graduate, and Professor Gyu-Jeong Noh of Seoul Asan Medical Center, has demonstrated the mechanism behind loss and recovery of consciousness through anesthesia, and detected the exact moment when a subject loses consciousness after being administered an anesthetic. Utilizing the analytic method called nonlinear dynamics which is used mainly to identify complex physical phenomena, Professor Kim’s team investigated the functional organization of brain activities in the conscious and anesthetized states. Recordings were obtained from 14 subjects who underwent induction of general anesthesia with propofol, and in the analysis, the team demonstrated that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of gamma waves, and that induction of general anesthesia with propofol reduces the capacity for information integration in the brain. Additionally captured was the moment the amount of information going from the frontal to the occipital lobes rapidly dropped, which coincided with loss of consciousness. The data congregated through the research directly supports the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia. The results of the study were published in the November 20, 2008 online issue of Consciousness and Cognition.

Regulation of Stomatal Response to Elevated CO2 Concentration by AtABCB14 (2008.9.7)

Climate change caused by increasing atmospheric CO2 is a major environmental problem of the 21st century. There has been much discussion about how to reduce CO2 output and prevent global warming. In this respect, plants are an important part of the overall picture as they are primary CO2 consumers and are directly challenged by increasing CO2 levels. Moreover, plants vary in their responses to elevated CO2. Plants that adapt better to this change are expected to out-compete their neighbors, which would cause instability in present ecosystems and unpredictable changes in weather and climate. In plants, CO2 uptake and water release occur through stomata. Stomata are formed by a pair of highly specialized epidermal cells, termed guard cells, and their opening and closing must be tightly controlled for optimal plant performance. It has been known for a long time that guard cells respond to high CO2 by closing their stomata. However, only recently have the molecular and cellular mechanisms for sensing and responding to high CO2 concentrations begun to be understood. CO2 is now known to have a direct effect on guard cells and to elicit stomatal closing through complex molecular interactions between currently ill-defined positive and negative factors. Our research into the role of ABC transporters in guard cell regulation resulted in the identification of an ABCB-type ABC transporter that is strongly expressed in guard cells and localized at the plasma membrane. We observed in intact leaves that, under elevated CO2 conditions, deletion mutants of AtABCB14 closed their stomata more rapidly than their wild-type counterparts, whereas AtABCB14-overexpressing mutants closed their stomata only partially. Further detailed analyses using E. coli and HeLa cell revealed that AtABCB14 plays a role as a malate importer. Thus, we conclude that AtABCB14 negatively regulates stomatal movement by transporting malate into the guard cell under elevated CO2 condition. These results are entirely novel and have strong implications for our current knowledge about the regulation of pore size under high CO2 condition. A topic that has not alone major repercussions for basic plant science but also for agriculture, especially within the perspective of rising atmospheric CO2 concentrations and the need to assure adequate food production for future generations. In addition, these results are very exciting for the broad and diverse ABC transporter community which is composed of scientists studying ABC transporters in all kingdoms of life, from prokaryotes to human. According to the reports up to now, ABC proteins of the same sub-family have similar functions and their functions are conserved between organisms also. In fact, many functional studies of genes were performed using homology with already identified genes. Thus, our studies may be helpful for identifying unknown roles of ABC proteins, and provide clues to solve the functions of animal ABC proteins for which the mutants are difficult to obtain. Professor Youngsook Lee Department of Life Science Tel: +82-54-279-8185 Fax: +82-54-279-2199 Email: ylee@postech.ac.kr Dr. Miyoung Lee Department of Life Science Tel: +82-54-279-5980 Fax: +82-54-279-2199 E-mail: anny98@postech.ac.kr

Metal Atom Chains on Graphene Nanoribbons (2008.12.31)

Professor Seung-Hoon Jhi and Ph.D. Candidate Seon-Myeong Choi, both of the Department of Physics, in their study of metal doped graphene nanoribbons, discovered that the adsorbed metal atoms form atomic chains which can be used as reagents to identify the edge atomic structures of the graphene nanoribbons and also as gate-driven spin valves to control the spin current in graphene nanoribbons. Graphene, the basic structural element of all graphitic materials including graphite, carbon nanotubes and fullerenes, is a one-atom-thick planar sheet of carbon atoms that are densely packed in a honeycomb crystal lattice. Placed in layers on top of each other, it would take 200,000 membranes to reach high enough to match the thickness of a human hair. Graphene nanostructures have attracted great attention due to their unique and intriguing electronic and transport properties. Particularly, the graphene nanoribbons’ carrier mobility is very promising for high-speed electronic devices. Professor Jhi’s team studied electronic and magnetic properties of alkali and alkaline-earth metal doped graphene nanoribbons by the pseudopotential density functional method. The findings are that strong site dependence is observed in metal adsorption on graphene nanoribbons, and that the adsorbed metal atoms are found to spontaneously form atomic chains at the edges of zigzag-edged graphene nanoribbons. The self-assembled atomic chains can be used to analyze the atomic structures of the graphene nanoribbon edges, which had proved difficult due to the extreme thinness of graphene. Also, such doped graphene nanoribbons exhibited intriguing magnetic properties such as hysteresis and spin compensation as metal atoms switch from one edge to another at alternating gate voltages. Using this phenomenon, the research team suggested a schematic model for the spin-valve structure that drives alkali metal atoms from one edge of a zigzag-edged graphene nanoribbon to the other. The research outcomes were presented in the December 31, 2008 issue of Physical Review Letters.

Structure and Mechanism of MukBEF Condensin Deciphered (2009.1.9)

A research team of Department of Life Science’s Center for Biomolecular Recognition and Division of Molecular and Life Science, consisting of Professor Byung-Ha Oh, Doctor Jae-Sung Woo, and Doctor Jae-Hong Lim, has solved secrets of the ring-shaped molecular structure of the MukBEF condensin, the key mediator of chromosome condensation. In eukaryotic organisms, chromosomes are found in the nucleus of every cell. Before cell division, chromosomes are condensed, and the two replicated copies of the chromosomes are partitioned into the two daughter cells. In prokaryotic organisms, chromosome condensation also takes place to insure partitioning of the replicated chromosomal copies into two newly divided cells. Chromosomes are long DNA molecules, ~1,000-10,000 times longer than the size of normal cells. How such a huge molecule can fit into a small volume in a cell and how the cell can divide replicated chromosomes into two exact halves without tangling and tearing is still a baffling mystery. Chromosome condensation is a well-known phenomenon, even mentioned in middle and high school textbooks, but the underlying mechanisms have been elusive. Professor Oh’s team brought to light the protein complex’s molecular structure as well as the functional mechanism. The findings are also expected to be utilized in applied research for development of antibiotics or anticancer substances, since cells cannot grow normally when chromosome condensation is hindered. The research outcomes were presented in the January 9, 2009 online issue of Cell. “This is only the beginning of research in the chromosome condensation area,” evaluated Professor Oh, declaring the team’s plans to continue research in condensation mechanism in eukaryotic cells which have more than one chromosome. He added that compared to prokaryotic cells, “condensation in eukaryotic cells is estimated to be controlled by much more intricate mechanisms because each chromosome is condensed separately.”

High Quality Ferroelectric Memory with Tb/In2 Density Realized by Nanotechnology (2008.6.15)

Ajoint research between POSTECH (Pohang University of Science and Technology) and Max Planck Institute of Microstructure Physics, Halle, has produced an advanced technology applicable to the development of the permanent memory, FeRAM, which can save 176 billion bits per square inch (published in Nature Nanotechnology, vol. 3, page 402). FeRAM has attracted many researchers’ interest because of its excellent characters such as nonvolatility, fast read and write, and high reliability. However, limitation in realizing large scale integration of ferroelectrics on a single chip has hindered the wide applications of FeRAM. In order to achieve the density of terabit per square inch, the size of ferroelectrics must be less than 25nm. It is well known that ferroelectric properties could be vanished if the size of ferroelectrics reduces down to nano scales: the size effect. Therefore, it is necessary to not only develop a novel method to fabricate nano-sized ferroelectrics, but also to investigate the intrinsic size effects of ferroelectrics in order for the widespread use of the computers containing memories with ultra high density, no booting, and no refresh process to be advanced. In this sense, the development of 65nm sized metal (Pt) - ferroelectric (PZT) - metal (Pt) nanocapacitors is a valuable work for the potential applications of FeRAM. Metal-ferroelectric-metal nanocapacitors were fabricated by stencil method using ultra-thin anodic alumina mask with honeycomb arrayed 65nm sized pores. Firstly, an aluminum plate was electrochemically oxidized. In this process, the 65nm sized pores were self-ordered. When the aluminum is shaped with a punch beforehand, the pores arrange themselves in a completely regular pattern. The anodic alumina mask was then transferred to platinum coated magnesium oxide substrate. By taking advantage of excellent thermal stability of anodic alumina, ferroelectric materials as well as electrode materials could be deposited into the extremely tiny pores at a high temperature. During the entire process, there was no thermal treatment nor use of chemicals or physical damages, resulting in high quality nanocapacitors. By removing the mask after deposition of platinum top electrode material, 176 billion bits per square inch of Pt-PZT-Pt nanocapacitors were obtained. In principle, other materials could be used as well for the ferroelectrics and electrodes as fatigue free capacitors. The success of this project is due to the fruitful Korea- Germany cooperation. The project was supported by the Korea Research Foundation, the ‘Brain Korea 21 Program’, the Volkswagen Foundation, and the German Research Foundation. Professor Sunggi Baik Department of Materials Science and Engineering Tel: +82-54-279-2001 Fax: +82-54-279-2709 E-mail:sgbaik@postech.ac.kr