演 題:" Epb41l5, a Mind Bomb 1 Interacting Protein, Promotes Neuronal Differentiation by Facilitating Disassembly of Apical Junctional Complexes"

演 者:Miho Matsuda, PhD
Laboratory of Molecular Genetics, NICHD, NIH, Bethesda, MD 20892, USA
要 旨: 
Notch signaling plays a critical role in cell fate specification and a failure of Notch signaling can lead to birth defects and cancer metastasis. Mind bomb 1 (Mib1), an E3 ubiquitin ligase, ubiquitylates Notch ligand Delta and triggers its endocytosis, which is an essential step for effective Notch activation. In this study we identified Erythrocyte membrane Protein Band 4.1-like 5 (Epb41l5) as a Mib1 interacting protein. While Epb41l5 is localized at the plasma membrane and can recruit Mib1 to the cell surface, its loss does not significantly alter the subcellular distribution of DeltaD protein or alter the pattern of early neurogenesis in zebrafish embryos. It suggests that Epb41l5 is not essential for Mib-mediated Delta endocytosis and subsequent Notch activation. Nevertheless, at one-day post fertilization when neuroepithelial cells acquire more prominent apical-basal polarity, neuronal cell differentiation is delayed and the differentiating/differentiated neurons are mislocalized in the hindbrain of epb41l5 deficient embryos. This delay in neuronal differentiation may be related to a role of Epb41l5 in facilitating epithelial-mesenchymal transition by promoting disassembly of apical junctional complexes. After specification of neuronal cell fates, neuronal progenitors need to disassemble apical junctional complexes, delaminate, and translocate to the basal side of the neuroepithelium to complete differentiation. We show that when epb41l5 function is lost, there is an aberrant persistence of junctional complexes made by neuronal progenitors and this delays their differentiation. Furthermore, Mib1 ubiquitylates Epb41l5 and promotes its degradation, which may ultimately stabilize apical junctional complex. Since Mib1 regulates Notch-mediated cell fate specification, our results propose that Mib1 might be a dual regulator of Notch-mediated neuronal cell fate specification and subsequent neuronal differentiation.

日 時: 2011年10月3日(月) 

場 所:  15号館1階 15102セミナー室

世話人: 生命システム学科  


演 題:"Collagen and the regulation of platelet function: a precarious balance between bleeding and thrombosis"

演 者:Jonathan Gibbins. PhD
Professor of Cell Biology
Institute for Cardiovascular and Metabolic Research
School of Biological Sciences
University of Reading
Whiteknights Reading, UK

日 時: 2011年7月29日(金)午後4時〜5時

場 所:  15号館1階 15102セミナー室

世話人: 生命システム学科  

要旨:Platelets perform an important function, triggering the blood to clot following injury, but may also be activated and trigger thrombosis in diseased arteries. In recent years substantial progress has been made in understanding how platelets recognise and respond to tissue injury or diseased vessels, yet ignore the un-damaged vasculature. This has begun to feed into the design of new strategies for the prevention of thrombosis, through the suppression of platelet reactivity - anti-platelet therapy. The balance between activatory and inhibitory signalling in the platelet determines the outcome of a precarious balance between haemostasis and thrombosis.
In this talk the role of collagen, as a principal activatory platelet agonist will be introduced, along with the multi-receptor mechanisms than enable platelet responses to collagens exposed at sites of vascular injury that culminate in haemostasis. This will include a surprising new role for the chaperone protein HSP47 on the surface of these cells. Platelet activatory cell signalling is tempered by opposing inhibitory signalling, and we have recently made advances in understanding how inhibitory receptors reduce platelet reactivity . At the heart of activatory and inhibitory platelet regulation lies immunoreceptor signalling mechanisms that will be explored.


演 題:Identification of peptide sequences that inhibit their own translation

演 者:Dr. Allen Buskirk (Department of Chemistry and Biochemistry, Brigham Young University, U.S.A.)

日 時: 2011年6月21日(火) 午後3時30分~4時30分

場 所:  15号館1階 15102セミナー室

世話人: 生命システム学科 伊藤維昭

大腸菌遺伝学を巧みに利用して、リボソームが翻訳を苦手とするアミノ酸配列 を新たに創り出すという研究で、翻訳やゲノム配列のあり方などに示唆深いお 話になりそうです。

While the ribosome can synthesize a vast array of protein sequences, its sequence independence is not entirely universal. Several proteins inhibit the ribosome during their own translation. In bacteria, leader peptides that induce stalling can regulate the expressionof downstream genes on the same mRNA. Stalling on the SecM peptide, for example, regulates SecA expression in response to the levels of activity of the secretion machinery. With only about four essential residues, such peptides share little similarity and interact with the ribosome by different mechanisms. To explore the scope of regulation by stalling peptides and further study the mechanism of stalling, we identified and characterized new examples from random libraries. We previously developed a genetic selection that ties stalling to the life of the cell. Our selection relies on the natural bacterial system that rescues arrested ribosomes. Here we report a second generation selection capable of identifying stalling peptides of various lengths and sequence composition and the characterization of several novel stalling peptides. We conclude that ribosome stalling is caused by numerous sequences and is more common than previously believed.


演 題:高等植物の生殖にかかわるpentatricopeptide repeat遺伝子の進化

演 者:藤井壮太 博士 (京都大学理学研究科 JSPS特別研究員)

日 時: 2011年6月10日 午後4時〜5時

場 所:  16号館2階16203会議室

要 旨: Pentatricopeptide repeat (PPR)は真核生物特有の遺伝子ファミリーであり,高等植物では進化の過程において50-100倍の規模に数を増やしている.近年の研究により,PPRタンパク質のほとんどがミトコンドリアか葉緑体において様々な転写後RNA修飾プロセスに関わっている事が明らかとなってきた.本発表では20種を越える植物種の比較解析からPPRタンパク質の進化とオルガネラとの共生について考察する.さらにPPRのうち,特に生殖メカニズムに関わるサブクラスについての塩基配列解析の結果から,高等植物の生殖とミトコンドリアとの関係について現在の考えを紹介する.

世話人: 生命資源環境学科 河邊昭


演 題:平らな葉を縮れ葉にしてわかったこと

演 者: 小山 知嗣 博士 (京都大学大学院生命科学研究科・特命助教)

日 時:   2011年5月13日 午後4時〜5時

場 所:  16号館2階16203会議室

要 旨: 私は植物の葉の発生や形態の多様性について興味をもって研究を進めています。本セミナーでは、植物に保存されたTCP遺伝子群に着目した研究を紹介します。まず、シロイヌナズナTCP遺伝子の機能を阻害したところ、破壊された遺伝子数に応じて、葉の形態が段階的に縮れることがわかりました。逆に、TCP遺伝子を過剰に作用させたところ、野生型で認められる鋸歯(きょし、葉の縁のギザギザ)がなくなり、平らな縁を形成することが明らかになりました。興味深い事に、TCP遺伝子の機能阻害により、花弁が縮れることも明らかになっており、フリンジ咲き花き植物の作出が試みられています。


世話人:       生命資源環境学科   木村成介